Method for producing cell product, method for purifying cell product, method for suppressing decrease in membrane permeability of cell product, system for producing cell product, and system for purifying cell product

Abstract

Provided is a method for producing a cell product, the method comprising obtaining a cell product by filtering a cell culture medium through a porous membrane, wherein: the porous membrane has a liquid contact surface having at least one selected from the group consisting of an aperture ratio of 57.5% or less, a pore diameter having a variation coefficient of 0.5 or less, and a pore diameter / fiber diameter of 1.3 or less; the liquid contact surface has at least one selected from the group consisting of a structural anisotropy of 0.97-1.03 and a long diameter / short diameter of a hole of 1.8 or less; and the shear stress due to the flow of the culture medium on the liquid contact surface is 4.0 N / m2 or less.

Description

Method for producing cell products, method for purifying cell products, method for suppressing a decrease in membrane permeability of cell products, system for producing cell products, and system for purifying cell products

[0001] The present invention relates to filtration technology, and to a method for producing a cell product, a method for purifying a cell product, a method for suppressing a decrease in membrane permeability of a cell product, a system for producing a cell product, and a system for purifying a cell product.

[0002] Cell culture technology is essential for the production of various biopharmaceuticals, such as antibodies, growth hormones, and insulin, and has contributed greatly to the advancement of medicine in recent years. Among biopharmaceuticals, antibody drugs in particular have attracted attention. Highly efficient and stable production of monoclonal antibodies by culturing antibody-producing cells is one of the most important industrial themes.

[0003] Industrial cell culture methods for producing useful cellular products such as antibodies can be broadly classified into two types: adherent culture and suspension culture. In adherent culture, cells adhere to the inner surface of a culture vessel. In suspension culture, cells are suspended in a culture solution. Of these, suspension culture is the mainstream due to its ease of scale-up and control on a large scale.

[0004] In methods for culturing cells by suspension culture, for example, a stirring mechanism has been proposed in a culture vessel such as a spinner flask to suspend the cells, and the stirring mechanism may be a magnetic stirrer or a mechanically driven shaft-shaped impeller. However, in conventional suspension culture methods, cells are cultured without replenishment of nutrients, and growth inhibitors such as lactic acid may accumulate. As a result, the cell growth rate may stop when the cell density is low.

[0005] In contrast, in suspension culture methods, a method has been proposed for culturing cells at high density and in large quantities to continuously produce cell products with high efficiency. This method involves supplying fresh culture medium to a culture vessel at a constant rate while filtering and discharging old culture medium containing cell products out of the culture vessel at a constant rate. This type of culture is generally called continuous culture or perfusion culture (see, for example, Patent Documents 1 to 5). In continuous culture, the amount of culture medium supplied to the culture vessel can be controlled to be equal to the amount of culture medium discharged from the culture vessel. What is important in continuous culture is to efficiently separate the cells in the culture medium from the old culture medium and cell products over a long period of time, remove the old culture medium and cell products from the culture vessel, and maintain the cell growth environment in the culture vessel under optimal conditions for a long period of time.

[0006] Japanese Patent Application Laid-Open No. 2018-76291 Japanese Patent Application Laid-Open No. 2009-45019 Japanese Patent Application Laid-Open No. 2021-48776 Japanese Patent No. 5696479 Japanese Patent Application Laid-Open No. 2022-516516

[0007] In continuous culture, porous membranes are used to separate cells in the culture medium in a culture tank from old culture medium and cell products. However, as filtration time through a porous membrane accumulates, fouling occurs, with substances depositing or adhering to the surface and pores of the porous membrane, resulting in a decrease in the permeability of the cell products through the porous membrane. Therefore, the present invention aims to provide a method for producing a cell product, a method for purifying a cell product, a method for suppressing a decrease in the membrane permeability of a cell product, a system for producing a cell product, and a system for purifying a cell product, all of which are capable of suppressing a decrease in the permeability of the cell product through the porous membrane.

[0008] [1] A method for producing a cell product by filtering a cell culture solution through a porous membrane, wherein the porous membrane has a liquid-contacting surface having at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the shear stress due to the flow of the culture solution on the liquid-contacting surface is 4.0 N / m２A method for producing a cell product, wherein the liquid-contacting surface has an opening rate of 57.5% or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 to 1.03. In the method for producing a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 to 1.03. In the method for producing a cell product, the liquid-contacting surface may have a pore size / fiber diameter ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 to 1.03. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 to 1.03. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size ratio of 1.3 or less, and a structural anisotropy of 0.97 to 1.03. In the method for producing a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a pore size / fiber size ratio of 1.3 or less, and a structural anisotropy of 0.97 to 1.03. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and ... and a pore major axis / minor axis ratio of 1.8 or less. In the method for producing a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less. In the method for producing a cell product, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less.In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter / fiber diameter of 1.3 or less, and a pore major axis / minor axis ratio of 1.8 or less. In the method for producing a cell product, the liquid-contacting surface may have a pore diameter with a coefficient of variation of 0.5 or less, a pore diameter / fiber diameter of 1.3 or less, and a pore major axis / minor axis ratio of 1.8 or less. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, and a pore diameter / fiber diameter of 1.3 or less, and a pore major axis / minor axis ratio of 1.8 or less. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, and a pore diameter / fiber diameter of 1.3 or less, and a pore major axis / minor axis ratio of 1.8 or less. In the method for producing a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less. In the method for producing a cell product, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less. In the method for producing a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter / fiber diameter of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less. In the method for producing a cell product, the liquid-contacting surface may have a pore diameter with a coefficient of variation of 0.5 or less, and a pore diameter / fiber diameter of 1.3 or less, and a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less.In the method for producing the cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and a pore major axis / minor axis ratio of 1.8 or less.

[0009] [2] The method for producing a cell product according to [1], wherein the porous membrane has at least one selected from the group consisting of an average pore size of 1 μm or more at the liquid-contacting surface and maximum / minimum values ​​of the average pore size in three or more film thickness directions. In the method for producing a cell product, the porous membrane may have an average pore size of 1 μm or more at the liquid-contacting surface. In the method for producing a cell product, the porous membrane may have maximum / minimum values ​​of the average pore size in three or more film thickness directions. In the method for producing a cell product, the porous membrane may have an average pore size of 1 μm or more at the liquid-contacting surface and maximum / minimum values ​​of the average pore size in three or more film thickness directions.

[0010] [3] The method for producing a cell product according to [1], wherein the porous membrane has at least one selected from the group consisting of an average pore size of 10 μm or less at the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface. In the method for producing a cell product, the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.

[0011] [4] The method for producing a cell product according to [2], wherein the porous membrane is a hollow fiber membrane.

[0012] [5] A method for producing a cell product according to [4], wherein the hollow fiber membrane has a gradient structure in which the average pore size decreases from the primary side to the secondary side in the membrane thickness direction.

[0013] [6] A method for producing a cell product according to [4] or [5], wherein the blocking pore size of the pores in the hollow fiber membrane is 0.05 μm or more and 20 μm or less.

[0014] [7] A method for producing a cell product according to any one of [4] to [6], wherein the hollow fiber membrane is made of a synthetic polymer membrane.

[0015] [8] The method for producing a cell product according to [7], wherein the synthetic polymer is polysulfone.

[0016] [9] A method for producing a cell product according to any one of [4] to [8], wherein the hollow fiber membrane has a coarse layer and a dense layer.

[0017]

[10] The density of cells contained in the culture medium to be filtered is 5 × 10 ７ The method for producing a cell product according to any one of [2] or [4] to [9], wherein the cell concentration is 0.01 to 0.01 cells / mL or less.

[0018]

[11] The method for producing a cell product according to [3], wherein the porous membrane is a hollow fiber membrane.

[0019]

[12] The method for producing a cell product according to

[11] , wherein the hollow fiber membrane has a substantially uniform structure in the membrane thickness direction from the primary side to the secondary side.

[0020]

[13] The method for producing a cell product according to

[11] or

[12] , wherein the blocking pore size of the pores in the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

[0021]

[14] The method for producing a cell product according to any one of

[11] to

[13] , wherein the hollow fiber membrane is made of a synthetic polymer membrane.

[0022]

[15] The method for producing a cell product according to

[14] , wherein the synthetic polymer is polyvinylidene fluoride.

[0023]

[16] The density of cells contained in the culture medium to be filtered is 8 × 10 ７ The method for producing a cell product according to any one of [3] or

[11] to

[15] , wherein the concentration of the cell product is 1000 cells / mL or more.

[0024]

[17] The shear stress was measured based on the viscosity of the culture medium, and the measured shear stress was 4.0 N / m２ The method for producing a cell product described in any one of [1] to

[16] , further comprising controlling the flow rate of the culture solution filtered through the porous membrane in a direction parallel to the membrane surface so as to be as follows:

[0025]

[18] The method for producing a cell product according to any one of [1] to

[17] , wherein the culture medium that has not been filtered through the hollow fiber membrane is returned to the cell culture tank.

[0026]

[19] The method for producing a cell product according to any one of [1] to

[18] , wherein the product is an antibody.

[0027]

[20] The method for producing a cell product according to any one of [1] to

[19] , wherein the cells are perfusion cultured.

[0028]

[21] A method for purifying a cell product by filtering a cell culture solution through a porous membrane, wherein the porous membrane has a liquid-contacting surface having at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the shear stress due to the flow of the culture solution on the liquid-contacting surface is 4.0 N / m ２A method for purifying a cell product, wherein the liquid-contacting surface has an opening rate of 57.5% or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 to 1.03. In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 to 1.03. In the method for purifying a cell product, the liquid-contacting surface may have a pore size / fiber diameter ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 to 1.03. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 to 1.03. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size ratio of 1.3 or less, and a degree of structural anisotropy of 0.97 to 1.03. In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a pore size / fiber size ratio of 1.3 or less, and a degree of structural anisotropy of 0.97 to 1.03. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and a degree of structural anisotropy of 0.97 to 1.03. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and a degree of structural anisotropy of 0.97 to 1.03. In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less. In the method for purifying a cell product, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less. In the method for purifying a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less.In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter / fiber diameter of 1.3 or less, and a pore major axis / minor axis ratio of 1.8 or less. In the method for purifying a cell product, the liquid-contacting surface may have a pore diameter with a coefficient of variation of 0.5 or less, a pore diameter / fiber diameter of 1.3 or less, and a pore major axis / minor axis ratio of 1.8 or less. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, and a pore diameter / fiber diameter of 1.3 or less, and a pore major axis / minor axis ratio of 1.8 or less. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, and a pore diameter / fiber diameter of 1.3 or less, and a pore major axis / minor axis ratio of 1.8 or less. In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less. In the method for purifying a cell product, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less. In the method for purifying a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter / fiber diameter ratio of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less. In the method for purifying a cell product, the liquid-contacting surface may have a pore diameter with a coefficient of variation of 0.5 or less, and a pore diameter / fiber diameter ratio of 1.3 or less, and a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less.In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less.

[0029]

[22] The method for purifying a cell product according to

[21] , wherein the porous membrane has at least one selected from the group consisting of an average pore size of 1 μm or more at the liquid-contacting surface and maximum / minimum values ​​of the average pore size in three or more film thickness directions. In the method for purifying a cell product, the porous membrane may have an average pore size of 1 μm or more at the liquid-contacting surface. In the method for purifying a cell product, the porous membrane may have maximum / minimum values ​​of the average pore size in three or more film thickness directions. In the method for purifying a cell product, the porous membrane may have an average pore size of 1 μm or more at the liquid-contacting surface and maximum / minimum values ​​of the average pore size in three or more film thickness directions.

[0030]

[23] The method for purifying a cell product according to

[21] , wherein the porous membrane has at least one selected from the group consisting of an average pore size of 10 μm or less at the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface. In the method for purifying a cell product, the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.

[0031]

[24] The method for purifying a cell product according to

[22] , wherein the porous membrane is a hollow fiber membrane.

[0032]

[25] The method for purifying a cell product according to

[24] , wherein the hollow fiber membrane has a gradient structure in which the average pore size decreases from the primary side to the secondary side in the membrane thickness direction.

[0033]

[26] The method for purifying a cell product according to

[24] or

[25] , wherein the pores of the hollow fiber membrane have a blocking pore size of 0.05 μm or more and 20 μm or less.

[0034]

[27] The method for purifying a cell product according to any one of

[24] to

[26] , wherein the hollow fiber membrane is made of a synthetic polymer membrane.

[0035]

[28] The method for purifying a cell product according to

[27] , wherein the synthetic polymer is polysulfone.

[0036]

[29] The method for purifying a cell product according to any one of

[24] to

[28] , wherein the hollow fiber membrane has a coarse layer and a dense layer.

[0037]

[30] The density of cells contained in the culture medium to be filtered is 5 × 10 ７ The method for purifying a cell product according to any one of

[22] or

[24] to

[29] , wherein the concentration of the cell product is 1000 or less cells / mL.

[0038]

[31] The method for purifying a cell product according to

[23] , wherein the porous membrane is a hollow fiber membrane.

[0039]

[32] The method for purifying a cell product according to

[31] , wherein the hollow fiber membrane has a substantially uniform structure in the membrane thickness direction from the primary side to the secondary side.

[0040]

[33] The method for purifying a cell product according to

[31] or

[32] , wherein the blocking pore size of the pores in the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

[0041]

[34] The method for purifying a cell product according to any one of

[31] to

[33] , wherein the hollow fiber membrane is made of a synthetic polymer membrane.

[0042]

[35] The method for purifying a cell product according to

[34] , wherein the synthetic polymer is polyvinylidene fluoride.

[0043]

[36] The density of cells contained in the culture medium to be filtered is 8 × 10 ７ The method for purifying a cell product according to any one of

[23] or

[31] to

[35] , wherein the concentration of the cell product is 1000 or more cells / mL.

[0044]

[37] The shear stress was measured based on the viscosity of the culture medium, and the measured shear stress was 4.0 N / m ２ The method for purifying a cell product according to any one of

[21] to

[36] , further comprising controlling the flow rate of the culture solution filtered through the porous membrane in a direction parallel to the membrane surface so as to be as follows:

[0045]

[38] The method for purifying a cell product according to any one of

[21] to

[37] , wherein the culture medium that has not been filtered through the hollow fiber membrane is returned to the cell culture vessel.

[0046]

[39] The method for purifying a cell product according to any one of

[21] to

[38] , wherein the product is an antibody.

[0047]

[40] The method for purifying a cell product according to any one of

[21] to

[39] , wherein the cells are perfusion cultured.

[0048]

[41] A method for producing a cell product by filtering a cell culture solution through a porous membrane, wherein the porous membrane has a liquid-contacting surface having at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more, and the shear stress due to the flow of the culture solution on the liquid-contacting surface is 4.0 N / m ２A method for producing a cell product, wherein the liquid-contacting surface has an opening rate of 57.5% or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less. In the method for producing a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less. In the method for producing a cell product, the liquid-contacting surface may have a pore size / fiber diameter ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size ratio of 1.3 or less, and a structural anisotropy of 0.97 or less. In the method for producing a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a pore size / fiber size ratio of 1.3 or less, and a structural anisotropy of 0.97 or less. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and a structural anisotropy of 0.97 or less. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and a structural anisotropy of 0.97 or less. In the method for producing a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or more. In the method for producing a cell product, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or more. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or more. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber diameter of 1.3 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or more.In the method for producing a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or more. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or more. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the method for producing a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the method for producing a cell product, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, a degree of structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, a degree of structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter / fiber diameter of 1.3 or less, and a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the method for producing a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more.

[0049]

[42] The method for producing a cell product according to

[41] , wherein the porous membrane is a hollow fiber membrane.

[0050]

[43] The method for producing a cell product according to

[42] , wherein the hollow fiber membrane has a substantially uniform structure in the membrane thickness direction from the primary side to the secondary side.

[0051]

[44] The method for producing a cell product according to

[42] or

[43] , wherein the blocking pore size of the pores in the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

[0052]

[45] The method for producing a cell product according to any one of

[42] to

[44] , wherein the hollow fiber membrane is made of a synthetic polymer membrane.

[0053]

[46] The method for producing a cell product according to

[45] , wherein the synthetic polymer is polyvinylidene fluoride.

[0054]

[47] The shear stress was measured based on the viscosity of the culture medium, and the measured shear stress was 4.0 N / m ２ The method for producing a cell product described in any one of

[41] to

[46] , further comprising controlling the flow rate of the culture solution filtered through the porous membrane in a direction parallel to the membrane surface so that the above-mentioned condition is satisfied.

[0055]

[48] ​​The method for producing a cell product according to any one of

[41] to

[47] , wherein the culture medium that has not been filtered through the hollow fiber membrane is returned to the cell culture tank.

[0056]

[49] The method for producing a cell product according to any one of

[41] to

[48] , wherein the product is an antibody.

[0057]

[50] The method for producing a cell product according to any one of

[41] to

[49] , wherein the cells are perfusion cultured.

[0058]

[51] A method for purifying a cell product by filtering a cell culture solution through a porous membrane, wherein the porous membrane has a liquid-contacting surface having at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more, and the shear stress due to the flow of the culture solution on the liquid-contacting surface is 4.0 N / m ２A method for purifying a cell product, wherein the liquid-contacting surface has an opening rate of 57.5% or less, and a degree of structural anisotropy of 0.97 or less. In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a degree of structural anisotropy of 0.97 or less. In the method for purifying a cell product, the liquid-contacting surface may have a pore size / fiber diameter ratio of 1.3 or less, and a degree of structural anisotropy of 0.97 or less. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a degree of structural anisotropy of 0.97 or less. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size ratio of 1.3 or less, and a degree of structural anisotropy of 0.97 or less. In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a pore size / fiber size ratio of 1.3 or less, and a degree of structural anisotropy of 0.97 or less. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and a degree of structural anisotropy of 0.97 or less. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and a degree of structural anisotropy of 0.97 or less. In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or more. In the method for purifying a cell product, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or more. In the method for purifying a cell product, the liquid-contacting surface may have an aperture ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or more. In the method for purifying a cell product, the liquid-contacting surface may have an aperture ratio of 57.5% or less, a pore size / fiber diameter of 1.3 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or more.In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or more. In the method for purifying a cell product, the liquid-contacting surface may have an aperture ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or more. In the method for purifying a cell product, the liquid-contacting surface may have an aperture ratio of 57.5% or less, a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the method for purifying a cell product, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, a degree of structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, a degree of structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter / fiber diameter of 1.3 or less, and a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the method for purifying a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more.

[0059]

[52] The method for purifying a cell product according to

[51] , wherein the porous membrane is a hollow fiber membrane.

[0060]

[53] The method for purifying a cell product according to

[52] , wherein the hollow fiber membrane has a substantially uniform structure in the membrane thickness direction from the primary side to the secondary side.

[0061]

[54] The method for purifying a cell product according to

[52] or

[53] , wherein the blocking pore size of the pores in the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

[0062]

[55] The method for purifying a cell product according to any one of

[52] to

[54] , wherein the hollow fiber membrane is made of a synthetic polymer membrane.

[0063]

[56] The method for purifying a cell product according to

[55] , wherein the synthetic polymer is polyvinylidene fluoride.

[0064]

[57] The shear stress was measured based on the viscosity of the culture medium, and the measured shear stress was 4.0 N / m ２ The method for purifying a cell product according to any one of

[51] to

[56] , further comprising controlling the flow rate of the culture solution filtered through the porous membrane in a direction parallel to the membrane surface so that the above-mentioned flow rate is achieved.

[0065]

[58] The method for purifying a cell product according to any one of

[51] to

[57] , wherein the culture medium that has not been filtered through the hollow fiber membrane is returned to the cell culture vessel.

[0066]

[59] The method for purifying a cell product according to any one of

[51] to

[58] , wherein the product is an antibody.

[0067]

[60] The method for purifying a cell product according to any one of

[51] to

[59] , wherein the cells are cultured by perfusion.

[0068]

[61] A method for producing a cell product by filtering a cell culture solution through a porous membrane, wherein the porous membrane has a liquid-contacting surface having at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the shear stress due to the flow of the culture solution on the liquid-contacting surface is 4.0 N / m ２A method for suppressing a decrease in membrane permeability of a cellular product by making the following. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an opening rate of 57.5% or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size ratio of 1.3 or less, and a degree of structural anisotropy of 0.97 to 1.03. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and a degree of structural anisotropy of 0.97 to 1.03. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and a degree of structural anisotropy of 0.97 to 1.03. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less.In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore major axis / minor axis ratio of 1.8 or less. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size of 1.3 or less, and a pore major axis / minor axis ratio of 1.8 or less. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a pore size / fiber size of 1.3 or less, and a pore major axis / minor axis ratio of 1.8 or less. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, a degree of structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, a degree of structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter / fiber diameter of 1.3 or less, and a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less.In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less.

[0069]

[62] The method for suppressing a decrease in membrane permeability of a cellular product according to

[61] , wherein the porous membrane has at least one selected from the group consisting of an average pore size of 1 μm or more at the liquid-contacting surface and maximum / minimum values ​​of the average pore size in three or more thickness directions. In the method for suppressing a decrease in membrane permeability of a cellular product, the porous membrane may have an average pore size of 1 μm or more at the liquid-contacting surface. In the method for suppressing a decrease in membrane permeability of a cellular product, the porous membrane may have maximum / minimum values ​​of the average pore size in three or more thickness directions. In the method for suppressing a decrease in membrane permeability of a cellular product, the porous membrane may have an average pore size of 1 μm or more at the liquid-contacting surface and maximum / minimum values ​​of the average pore size in three or more thickness directions.

[0070]

[63] The method for suppressing a decrease in membrane permeability of a cellular product according to

[61] , wherein the porous membrane has at least one selected from the group consisting of an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cellular product, the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface. In the method for suppressing a decrease in membrane permeability of a cellular product, the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cellular product, the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10.

[0071]

[64] The method for suppressing a decrease in membrane permeability of a cell product according to

[62] , wherein the porous membrane is a hollow fiber membrane.

[0072]

[65] A method for suppressing a decrease in membrane permeability of a cell product according to

[64] , wherein the hollow fiber membrane has a gradient structure in which the average pore size decreases from the primary side to the secondary side in the membrane thickness direction.

[0073]

[66] A method for suppressing a decrease in membrane permeability of a cell product according to

[64] or

[65] , wherein the blocking pore size of the pores in the hollow fiber membrane is 0.05 μm or more and 20 μm or less.

[0074]

[67] A method for suppressing a decrease in membrane permeability of a cell product according to any one of

[64] to

[66] , wherein the hollow fiber membrane is made of a synthetic polymer membrane.

[0075]

[68] The method for suppressing a decrease in membrane permeability of a cell product according to

[67] , wherein the synthetic polymer is polysulfone.

[0076]

[69] The method for suppressing a decrease in membrane permeability of a cell product according to any one of

[64] to

[68] , wherein the hollow fiber membrane has a coarse layer and a dense layer.

[0077]

[70] The density of cells contained in the culture medium to be filtered is 5 × 10 ７ The method for suppressing a decrease in membrane permeability of a cell product according to any one of

[62] or

[64] to

[69] , wherein the cell product is present in an amount of 1000 to 10000 cells / mL or less.

[0078]

[71] The method for suppressing a decrease in membrane permeability of a cell product according to

[63] , wherein the porous membrane is a hollow fiber membrane.

[0079]

[72] A method for suppressing a decrease in membrane permeability of a cell product according to

[71] , wherein the hollow fiber membrane has a substantially uniform structure in the membrane thickness direction from the primary side to the secondary side.

[0080]

[73] A method for suppressing a decrease in membrane permeability of a cell product according to

[71] or

[72] , wherein the blocking pore size of the pores in the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

[0081]

[74] A method for suppressing a decrease in membrane permeability of a cell product according to any one of

[71] to

[73] , wherein the hollow fiber membrane is made of a synthetic polymer membrane.

[0082]

[75] The method for suppressing a decrease in membrane permeability of a cell product according to

[74] , wherein the synthetic polymer is polyvinylidene fluoride.

[0083]

[76] The density of cells contained in the culture medium to be filtered is 8 × 10 ７ The method for suppressing a decrease in membrane permeability of a cell product according to any one of

[63] or

[71] to

[75] , wherein the cell permeability is 100% or more of the above-mentioned cell products.

[0084]

[77] The shear stress was measured based on the viscosity of the culture medium, and the measured shear stress was 4.0 N / m ２ A method for suppressing a decrease in membrane permeability of a cell product according to any one of

[61] to

[76] , further comprising controlling the flow rate of the culture solution filtered through the porous membrane in a direction parallel to the membrane surface so as to be as follows:

[0085]

[78] The method for suppressing a decrease in membrane permeability of a cell product according to any one of

[61] to

[77] , wherein the culture medium not filtered through the hollow fiber membrane is returned to the cell culture vessel.

[0086]

[79] A method for suppressing a decrease in membrane permeability of a cell product according to any one of

[61] to

[78] , wherein the product is an antibody.

[0087]

[80] The method for suppressing a decrease in membrane permeability of a cell product according to any one of

[61] to

[79] , wherein the cells are cultured by perfusion.

[0088]

[81] A method for producing a cell product by filtering a cell culture solution through a porous membrane, wherein the porous membrane has a liquid-contacting surface having at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more, and the shear stress due to the flow of the culture solution on the liquid-contacting surface is 4.0 N / m ２A method for suppressing a decrease in membrane permeability of a cellular product by achieving the above. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an opening rate of 57.5% or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have a pore size / fiber diameter ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size ratio of 1.3 or less, and a structural anisotropy of 0.97 or less. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a pore size / fiber size ratio of 1.3 or less, and a structural anisotropy of 0.97 or less. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and a structural anisotropy of 0.97 or less. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore major axis / minor axis ratio of 1.8 or more. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or more. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or more.In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size of 1.3 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a pore size / fiber size of 1.3 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or more. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, a degree of structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, a degree of structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter / fiber diameter of 1.3 or less, and a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more.In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more.

[0089]

[82] The method for suppressing a decrease in membrane permeability of a cell product according to

[81] , wherein the porous membrane is a hollow fiber membrane.

[0090]

[83] A method for suppressing a decrease in membrane permeability of a cell product according to

[82] , wherein the hollow fiber membrane has a substantially uniform structure in the membrane thickness direction from the primary side to the secondary side.

[0091]

[84] A method for suppressing a decrease in membrane permeability of a cell product according to

[82] or

[83] , wherein the blocking pore size of the pores in the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

[0092]

[85] A method for suppressing a decrease in membrane permeability of a cell product according to any one of

[82] to

[84] , wherein the hollow fiber membrane is made of a synthetic polymer membrane.

[0093]

[86] The method for suppressing a decrease in membrane permeability of a cell product according to

[85] , wherein the synthetic polymer is polyvinylidene fluoride.

[0094]

[87] The shear stress was measured based on the viscosity of the culture medium, and the measured shear stress was 4.0 N / m ２ The method for suppressing a decrease in membrane permeability of a cell product according to any one of

[81] to

[86] , further comprising controlling the flow rate of the culture solution filtered through the porous membrane in a direction parallel to the membrane surface so that the above-mentioned rate is achieved.

[0095]

[88] The method for suppressing a decrease in membrane permeability of a cell product according to any one of

[81] to

[87] , wherein the culture medium not filtered through the hollow fiber membrane is returned to the cell culture vessel.

[0096]

[89] A method for suppressing a decrease in membrane permeability of a cell product according to any one of

[81] to

[88] , wherein the product is an antibody.

[0097]

[90] The method for suppressing a decrease in membrane permeability of a cell product according to any one of

[81] to

[89] , wherein the cells are cultured by perfusion.

[0098]

[91] A culture vessel for culturing cells, a porous membrane for filtering the cell culture solution to obtain a cell product, a pump for sending the culture solution from the culture vessel to the porous membrane, and a shear stress of 4.0 N / m due to the flow of the culture solution on the liquid-contacting surface of the porous membrane. ２and a control unit that controls the pump so that the liquid-contacting surface has at least one selected from the group consisting of an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber diameter ratio of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis ratio of 1.8 or less. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less and a structural anisotropy of 0.97 to 1.03. In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a structural anisotropy of 0.97 to 1.03. In the cell product production system, the liquid-contacting surface may have a pore size / fiber size ratio of 1.3 or less, and a degree of structural anisotropy of 0.97 to 1.03. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a degree of structural anisotropy of 0.97 to 1.03. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size of 1.3 or less, and a degree of structural anisotropy of 0.97 to 1.03. In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a pore size / fiber size of 1.3 or less, and a degree of structural anisotropy of 0.97 to 1.03. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less. In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less.In the cell product production system, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, and a pore major axis / minor axis of 1.8 or less. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, and a pore major axis / minor axis of 1.8 or less. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter / fiber diameter of 1.3 or less, and a pore major axis / minor axis of 1.8 or less. In the cell product production system, the liquid-contacting surface may have a pore diameter with a coefficient of variation of 0.5 or less, a pore diameter / fiber diameter of 1.3 or less, and a pore major axis / minor axis of 1.8 or less. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less. In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less. In the cell product production system, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, a degree of structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, a degree of structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter / fiber diameter of 1.3 or less, and a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less.In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less.

[0099]

[92] The cell product production system according to

[91] , wherein the porous membrane has at least one selected from the group consisting of an average pore size of 1 μm or more at the liquid-contacting surface and maximum / minimum values ​​of the average pore size in three or more film thickness directions. In the cell product production system, the porous membrane may have an average pore size of 1 μm or more at the liquid-contacting surface. In the cell product production system, the porous membrane may have maximum / minimum values ​​of the average pore size in three or more film thickness directions. In the cell product production system, the porous membrane may have an average pore size of 1 μm or more at the liquid-contacting surface and maximum / minimum values ​​of the average pore size in three or more film thickness directions.

[0100]

[93] The cell product production system according to

[91] , wherein the porous membrane has at least one selected from the group consisting of an average pore size of 10 μm or less at the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface. In the cell product production system, the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.

[0101]

[94] The cell product production system according to

[92] , wherein the porous membrane is a hollow fiber membrane.

[0102]

[95] A cell product manufacturing system according to

[94] , wherein the hollow fiber membrane has a gradient structure in which the average pore size decreases from the primary side to the secondary side in the membrane thickness direction.

[0103]

[96] A cell product manufacturing system according to

[94] or

[95] , wherein the blocking pore size of the pores in the hollow fiber membrane is 0.05 μm or more and 20 μm or less.

[0104]

[97] A cell product production system according to any one of

[94] to

[96] , wherein the hollow fiber membrane is made of a synthetic polymer membrane.

[0105]

[98] The system for producing a cell product according to

[97] , wherein the synthetic polymer is polysulfone.

[0106]

[99] A cell product manufacturing system according to any one of

[94] to

[98] , wherein the hollow fiber membrane has a coarse layer and a dense layer.

[0107]

[100] The density of cells contained in the culture medium to be filtered is 5 × 10 ７ The system for producing a cell product according to any one of

[92] or

[94] to

[99] , wherein the cell product concentration is 0.01 to 0.01 cells / mL or less.

[0108]

[101] The system for producing a cell product according to

[93] , wherein the porous membrane is a hollow fiber membrane.

[0109]

[102] A cell product production system according to

[101] , wherein the hollow fiber membrane has a substantially uniform structure in the membrane thickness direction from the primary side to the secondary side.

[0110]

[103] The system for producing a cell product according to

[101] or

[102] , wherein the blocking pore size of the pores in the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

[0111]

[104] A system for producing a cell product according to any one of

[101] to

[103] , wherein the hollow fiber membrane is made of a synthetic polymer membrane.

[0112]

[105] The system for producing a cell product according to

[104] , wherein the synthetic polymer is polyvinylidene fluoride.

[0113]

[106] The density of cells contained in the culture medium to be filtered is 8 × 10 ７ The system for producing a cell product according to any one of

[93] or

[101] to

[105] , wherein the cell product concentration is 100 cells / mL or more.

[0114]

[107] The control unit measures the shear stress based on the viscosity of the culture solution, and the measured shear stress is 4.0 N / m ２ A cell product manufacturing system according to any one of

[91] to

[106] , which controls the flow rate of the culture solution being filtered through the porous membrane in a direction parallel to the membrane surface so that:

[0115]

[108] A cell product manufacturing system according to any one of

[91] to

[107] , wherein the control unit receives input of data on the viscosity of the culture medium.

[0116]

[109] The cell product production system according to any one of

[91] to

[108] , further comprising a flow path for returning the culture solution that has not been filtered through the hollow fiber membrane to the culture tank.

[0117]

[110] A system for producing a cell product according to any one of

[91] to

[109] , wherein the product is an antibody.

[0118]

[111] The cell product production system according to any one of

[91] to

[110] , wherein the culture vessel cultures cells by perfusion.

[0119]

[112] A culture vessel for culturing cells, a porous membrane for filtering the cell culture solution to obtain a cell product, a pump for sending the culture solution from the culture vessel to the porous membrane, and a shear stress of 4.0 N / m due to the flow of the culture solution on the liquid-contacting surface of the porous membrane. ２and a control unit that controls the pump so that the liquid-contacting surface has at least one selected from the group consisting of an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a degree of structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less and a degree of structural anisotropy of 0.97 or less. In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a degree of structural anisotropy of 0.97 or less. In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a degree of structural anisotropy of 0.97 or less. In the cell product production system, the liquid-contacting surface may have a pore size / fiber size ratio of 1.3 or less and a degree of structural anisotropy of 0.97 or less. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a degree of structural anisotropy of 0.97 or less. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size of 1.3 or less, and a degree of structural anisotropy of 0.97 or less. In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a pore size / fiber size of 1.3 or less, and a degree of structural anisotropy of 0.97 or less. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, and a degree of structural anisotropy of 0.97 or less. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, and the pores may have a major axis / minor axis ratio of 1.8 or more. In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the pores may have a major axis / minor axis ratio of 1.8 or more.In the cell product production system, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter / fiber diameter of 1.3 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the cell product production system, the liquid-contacting surface may have a pore diameter with a coefficient of variation of 0.5 or less, a pore diameter / fiber diameter of 1.3 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or more. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, and a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber diameter of 1.3 or less, and a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more.In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more.

[0120]

[113] The system for producing a cell product according to

[112] , wherein the porous membrane is a hollow fiber membrane.

[0121]

[114] A cell product production system according to

[113] , wherein the hollow fiber membrane has a substantially uniform structure in the membrane thickness direction from the primary side to the secondary side.

[0122]

[115] A cell product production system according to

[113] or

[114] , wherein the blocking pore size of the pores in the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

[0123]

[116] A cell product production system according to any one of

[113] to

[115] , wherein the hollow fiber membrane is made of a synthetic polymer membrane.

[0124]

[117] The system for producing a cell product according to

[116] , wherein the synthetic polymer is polyvinylidene fluoride.

[0125]

[118] The control unit measures the shear stress based on the viscosity of the culture solution, and the measured shear stress is 4.0 N / m ２ A cell product production system according to any one of

[112] to

[117] , wherein the flow rate of the culture solution filtered through the porous membrane in a direction parallel to the membrane surface is controlled so as to achieve the above.

[0126]

[119] A cell product manufacturing system according to any one of

[112] to

[118] , wherein the control unit receives input of data on the viscosity of the culture medium.

[0127]

[120] The cell product production system according to any one of

[112] to

[119] , further comprising a flow path for returning the culture solution that has not been filtered through the hollow fiber membrane to the culture tank.

[0128]

[121] A system for producing a cell product according to any one of

[112] to

[120] , wherein the product is an antibody.

[0129]

[122] The cell product production system according to any one of

[112] to

[121] , wherein the culture vessel cultures cells by perfusion.

[0130]

[123] A culture vessel for culturing cells, a porous membrane for filtering the cell culture solution to purify the cell product, a pump for sending the culture solution from the culture vessel to the porous membrane, and a shear stress of 4.0 N / m due to the flow of the culture solution on the liquid-contacting surface of the porous membrane. ２and a control unit that controls the pump so that the liquid-contacting surface has at least one selected from the group consisting of an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber diameter ratio of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis ratio of 1.8 or less. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less and a structural anisotropy of 0.97 to 1.03. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a structural anisotropy of 0.97 to 1.03. In the cell product purification system, the liquid-contacting surface may have a pore size / fiber size ratio of 1.3 or less, and a degree of structural anisotropy of 0.97 to 1.03. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a degree of structural anisotropy of 0.97 to 1.03. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size ratio of 1.3 or less, and a degree of structural anisotropy of 0.97 to 1.03. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a pore size / fiber size ratio of 1.3 or less, and a degree of structural anisotropy of 0.97 to 1.03. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less.In the cell product purification system, the liquid-contacting surface may have a pore size / fiber size of 1.3 or less, and a pore major axis / minor axis ratio of 1.8 or less. In the cell product purification system, the liquid-contacting surface may have an aperture ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore major axis / minor axis ratio of 1.8 or less. In the cell product purification system, the liquid-contacting surface may have an aperture ratio of 57.5% or less, a pore size / fiber size of 1.3 or less, and a pore major axis / minor axis ratio of 1.8 or less. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a pore size / fiber size of 1.3 or less, and a pore major axis / minor axis ratio of 1.8 or less. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, and a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less. In the cell product purification system, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, a degree of structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, a degree of structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter / fiber diameter of 1.3 or less, and a degree of structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less.In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less. In the cell product purification system, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less.

[0131]

[124] The system for purifying a cell product according to

[123] , wherein the porous membrane has at least one selected from the group consisting of an average pore size of 1 μm or more at the liquid-contacting surface and maximum / minimum values ​​of the average pore size in three or more film thickness directions. In the system for purifying a cell product, the porous membrane may have an average pore size of 1 μm or more at the liquid-contacting surface. In the system for purifying a cell product, the porous membrane may have maximum / minimum values ​​of the average pore size in three or more film thickness directions. In the system for purifying a cell product, the porous membrane may have an average pore size of 1 μm or more at the liquid-contacting surface and maximum / minimum values ​​of the average pore size in three or more film thickness directions.

[0132]

[125] The system for purifying a cell product according to

[123] , wherein the porous membrane has at least one selected from the group consisting of an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the system for purifying a cell product, the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface. In the system for purifying a cell product, the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the system for purifying a cell product, the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.

[0133]

[126] The system for purifying a cell product according to

[124] , wherein the porous membrane is a hollow fiber membrane.

[0134]

[127] The system for purifying a cell product according to

[126] , wherein the hollow fiber membrane has a gradient structure in which the average pore size decreases from the primary side to the secondary side in the membrane thickness direction.

[0135]

[128] The system for purifying a cell product according to

[126] or

[127] , wherein the blocking pore size of the pores of the hollow fiber membrane is 0.05 μm or more and 20 μm or less.

[0136]

[129] The system for purifying a cell product according to any one of

[126] to

[128] , wherein the hollow fiber membrane is made of a synthetic polymer membrane.

[0137]

[130] The system for purifying a cell product according to

[129] , wherein the synthetic polymer is polysulfone.

[0138]

[131] The system for purifying a cell product according to any one of

[126] to

[130] , wherein the hollow fiber membrane has a coarse layer and a dense layer.

[0139]

[132] The density of cells contained in the culture medium to be filtered is 5 × 10 ７ The system for purifying a cell product according to any one of

[124] or

[126] to

[131] , wherein the cell product concentration is 0.01 to 0.15 cells / mL or less.

[0140]

[133] The system for purifying a cell product according to

[125] , wherein the porous membrane is a hollow fiber membrane.

[0141]

[134] The system for purifying a cell product according to

[133] , wherein the hollow fiber membrane has a substantially uniform structure in the membrane thickness direction from the primary side to the secondary side.

[0142]

[135] The system for purifying a cell product according to

[133] or

[134] , wherein the blocking pore size of the pores of the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

[0143]

[136] The system for purifying a cell product according to any one of

[133] to

[135] , wherein the hollow fiber membrane is made of a synthetic polymer membrane.

[0144]

[137] The purification system for a cell product according to

[136] , wherein the synthetic polymer is polyvinylidene fluoride.

[0145]

[138] The density of cells contained in the culture medium to be filtered is 8 × 10 ７ The system for purifying a cell product according to any one of

[125] or

[133] to

[137] , wherein the cell product concentration is 1000 or more cells / mL.

[0146]

[139] The control unit measures the shear stress based on the viscosity of the culture solution, and the measured shear stress is 4.0 N / m ２ A system for purifying a cell product according to any one of

[123] to

[138] , wherein the flow rate of the culture solution being filtered through the porous membrane in a direction parallel to the membrane surface is controlled so as to achieve the following:

[0147]

[140] The system for purifying a cell product according to any one of

[123] to

[139] , wherein the control unit receives input of data on the viscosity of the culture medium.

[0148]

[141] The system for purifying a cell product according to any one of

[123] to

[140] , further comprising a flow path for returning the culture solution that was not filtered through the hollow fiber membrane to the culture tank.

[0149]

[142] The system for purifying a cell product according to any one of

[123] to

[141] , wherein the product is an antibody.

[0150]

[143] The system for purifying a cell product according to any one of

[123] to

[142] , wherein the culture vessel cultures cells by perfusion.

[0151]

[144] A culture vessel for culturing cells, a porous membrane for filtering the cell culture solution to purify the cell product, a pump for sending the culture solution from the culture vessel to the porous membrane, and a shear stress of 4.0 N / m due to the flow of the culture solution on the liquid-contacting surface of the porous membrane. ２and a control unit that controls the pump so that the liquid-contacting surface has at least one selected from the group consisting of an aperture ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a degree of structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the cell product purification system, the liquid-contacting surface may have an aperture ratio of 57.5% or less and a degree of structural anisotropy of 0.97 or less. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a degree of structural anisotropy of 0.97 or less. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a degree of structural anisotropy of 0.97 or less. In the cell product purification system, the liquid-contacting surface may have a pore size / fiber size ratio of 1.3 or less and a degree of structural anisotropy of 0.97 or less. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a degree of structural anisotropy of 0.97 or less. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size of 1.3 or less, and a degree of structural anisotropy of 0.97 or less. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a pore size / fiber size of 1.3 or less, and a degree of structural anisotropy of 0.97 or less. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, and a degree of structural anisotropy of 0.97 or less. In the cell product purification system, the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore major axis / minor axis ratio of 1.8 or more. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a pore major axis / minor axis ratio of 1.8 or more.In the cell product purification system, the liquid-contacting surface may have a pore size / fiber size of 1.3 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the cell product purification system, the liquid-contacting surface may have an aperture ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the cell product purification system, the liquid-contacting surface may have an aperture ratio of 57.5% or less, a pore size / fiber size of 1.3 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a pore size / fiber size of 1.3 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or more. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, and a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the cell product purification system, the liquid-contacting surface may have a pore size / fiber size ratio of 1.3 or less, and a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber diameter of 1.3 or less, and a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more.In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and a structural anisotropy of 0.97 or less, and a pore major axis / minor axis ratio of 1.8 or more.

[0152]

[145] The system for purifying a cell product according to

[144] , wherein the porous membrane is a hollow fiber membrane.

[0153]

[146] The system for purifying a cell product according to

[145] , wherein the hollow fiber membrane has a substantially uniform structure in the membrane thickness direction from the primary side to the secondary side.

[0154]

[147] The system for purifying a cell product according to

[145] or

[146] , wherein the blocking pore size of the pores of the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

[0155]

[148] The system for purifying a cell product according to any one of

[145] to

[147] , wherein the hollow fiber membrane is made of a synthetic polymer membrane.

[0156]

[149] The purification system for a cell product according to

[148] , wherein the synthetic polymer is polyvinylidene fluoride.

[0157]

[150] The control unit measures the shear stress based on the viscosity of the culture solution, and the measured shear stress is 4.0 N / m ２ A system for purifying a cell product according to any one of

[144] to

[149] , wherein the flow rate of the culture solution being filtered through the porous membrane in a direction parallel to the membrane surface is controlled so as to achieve the above.

[0158]

[151] The system for purifying a cell product according to any one of

[144] to

[150] , wherein the control unit receives input of data on the viscosity of the culture medium.

[0159]

[152] The system for purifying a cell product according to any one of

[144] to

[151] , further comprising a flow path for returning the culture solution that was not filtered through the hollow fiber membrane to the culture tank.

[0160]

[153] The system for purifying a cell product according to any one of

[144] to

[152] , wherein the product is an antibody.

[0161]

[154] The system for purifying a cell product according to any one of

[144] to

[153] , wherein the culture vessel cultures cells by perfusion.

[0162]

[155] A method for obtaining a cell product by filtering a cell culture solution with a porous membrane, wherein the porous membrane has a liquid-contacting surface having at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane has at least one selected from the group consisting of an average pore size of 10 μm or less on the liquid-contacting surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10, and the density of cells contained in the culture solution to be filtered is 8×10 ７a method for producing a cell product, wherein the liquid-contacting surface has an opening ratio of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane has an average pore size at the liquid-contacting surface of 10 μm or less; a method for producing a cell product, wherein the liquid-contacting surface has a pore size coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane has an average pore size at the liquid-contacting surface of 10 μm or less; a method for producing a cell product, wherein the liquid-contacting surface has a pore size / fiber diameter ratio of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane has an average pore size at the liquid-contacting surface of 10 μm or less; In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface. In the method for producing a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface.In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface.In the method for producing a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for producing a cell product, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size of 1.3 or less, a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for producing a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a pore size / fiber size of 1.3 or less, a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface.In the method for producing a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface.In the method for producing a cell product, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid-contacting surface.In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid-contacting surface. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter / fiber diameter of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid-contacting surface.In the method for producing a cell product, the liquid-contacting surface may have a pore diameter with a coefficient of variation of 0.5 or less, and a pore diameter / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid-contacting surface. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface.In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the thickness direction of 1 to 10. In the method for producing the cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.In the method for producing a cell product, the liquid-contacting surface may have a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a degree of structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a degree of structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a degree of structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing the cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.In the method for producing a cell product, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have a pore diameter with an opening rate of 57.5% or less and a pore diameter with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and pore major axis / minor axis values ​​of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and pore major axis / minor axis values ​​of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.In the method for producing a cell product, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore diameter with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore diameter / fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have a pore diameter with a coefficient of variation of 0.5 or less, and a pore diameter / fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, and a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.In the method for producing a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have pore major axis / minor axis ratios of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have pore sizes with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have pore major axis / minor axis ratios of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less and a pore diameter with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and maximum / minimum values ​​of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and maximum / minimum values ​​of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.In the method for producing a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for producing a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.

[0163]

[156] The method for producing a cell product according to

[155] , wherein the porous membrane is a hollow fiber membrane.

[0164]

[157] The method for producing a cell product according to

[156] , wherein the hollow fiber membrane has a substantially uniform structure in the membrane thickness direction from the primary side to the secondary side.

[0165]

[158] The method for producing a cell product according to

[156] or

[157] , wherein the blocking pore size of the pores in the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

[0166]

[159] The method for producing a cell product according to any one of

[156] to

[158] , wherein the hollow fiber membrane is made of a synthetic polymer membrane.

[0167]

[160] The method for producing a cell product according to

[159] , wherein the synthetic polymer is polyvinylidene fluoride.

[0168]

[161] The method for producing a cell product according to any one of

[155] to

[160] , wherein the culture medium that has not been filtered through the hollow fiber membrane is returned to the cell culture tank.

[0169]

[162] The method for producing a cell product according to any one of

[155] to

[161] , wherein the product is an antibody.

[0170]

[163] The method for producing a cell product according to any one of

[155] to

[162] , wherein the cells are perfusion cultured.

[0171]

[164] A method for purifying a cell product by filtering a cell culture solution with a porous membrane, wherein the porous membrane has a liquid-contacting surface having at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane has at least one selected from the group consisting of an average pore size of 10 μm or less on the liquid-contacting surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10, and the density of cells contained in the culture solution to be filtered is 8×10 ７A method for purifying a cell product, wherein the liquid-contacting surface has an opening ratio of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane has an average pore size at the liquid-contacting surface of 10 μm or less. The method for purifying a cell product may also be characterized in that the liquid-contacting surface has a pore size coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane has an average pore size at the liquid-contacting surface of 10 μm or less. The method for purifying a cell product may also be characterized in that the liquid-contacting surface has a pore size / fiber diameter ratio of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane has an average pore size at the liquid-contacting surface of 10 μm or less. In the method for purifying a cell product, the liquid-contacting surface may have an aperture ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for purifying a cell product, the liquid-contacting surface may have an aperture ratio of 57.5% or less, a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less.In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less.In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for purifying a cell product, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size of 1.3 or less, a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface.In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface.In the method for purifying a cell product, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less at the liquid-contacting surface.In the method for purifying a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less at the liquid-contacting surface. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface.In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.In the method for purifying a cell product, the liquid-contacting surface may have a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a degree of structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a degree of structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a degree of structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have pore major axis / minor axis ratios of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have pore major axis / minor axis ratios of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.In the method for purifying a cell product, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have a pore diameter with a coefficient of variation of 57.5% or less and a pore diameter with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.In the method for purifying a cell product, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore diameter / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have a pore diameter with a coefficient of variation of 0.5 or less, and a pore diameter / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have pore major axis / minor axis ratios of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have pore sizes with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have pore major axis / minor axis ratios of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, and the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore diameter with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.In the method for purifying a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for purifying a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.

[0172]

[165] The method for purifying a cell product according to

[164] , wherein the porous membrane is a hollow fiber membrane.

[0173]

[166] The method for purifying a cell product according to

[165] , wherein the hollow fiber membrane has a substantially uniform structure in the membrane thickness direction from the primary side to the secondary side.

[0174]

[167] The method for purifying a cell product according to

[165] or

[166] , wherein the pores of the hollow fiber membrane have a blocking pore size of 0.05 μm or more and 10 μm or less.

[0175]

[168] The method for purifying a cell product according to any one of

[165] to

[167] , wherein the hollow fiber membrane is made of a synthetic polymer membrane.

[0176]

[169] The method for purifying a cell product according to

[168] , wherein the synthetic polymer is polyvinylidene fluoride.

[0177]

[170] The method for purifying a cell product according to any one of

[165] to

[169] , wherein the culture medium that has not been filtered through the hollow fiber membrane is returned to the cell culture vessel.

[0178]

[171] The method for purifying a cell product according to any one of

[164] to

[170] , wherein the product is an antibody.

[0179]

[172] The method for purifying a cell product according to any one of

[164] to

[171] , wherein the cells are cultured by perfusion.

[0180]

[173] A method for obtaining a cell product by filtering a cell culture solution with a porous membrane, wherein the porous membrane has a liquid-contacting surface having at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane has at least one selected from the group consisting of an average pore size of 10 μm or less on the liquid-contacting surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10, and the density of cells contained in the culture solution to be filtered is 8×10 ７cells / mL or more, thereby suppressing a decrease in membrane permeability of cellular products. In the method for suppressing a decrease in membrane permeability of cellular products, the liquid-contacting surface may have an opening rate of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for suppressing a decrease in membrane permeability of cellular products, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for suppressing a decrease in membrane permeability of cellular products, the liquid-contacting surface may have a pore size / fiber diameter ratio of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface.In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber diameter of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a pore size / fiber diameter ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less.In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less and a pore size / fiber diameter ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less.In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an aperture ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface having a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane having an average pore size at the liquid-contacting surface of 10 μm or less. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an aperture ratio of 57.5% or less, a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface having a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane having an average pore size at the liquid-contacting surface of 10 μm or less. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface having a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane having an average pore size at the liquid-contacting surface of 10 μm or less. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 μm or less.In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an opening rate of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface.In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore diameter / fiber diameter ratio of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less at the liquid-contacting surface.In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less at the liquid-contacting surface. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less.In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface.In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10.In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an aperture ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an aperture ratio of 57.5% or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have a pore size with a coefficient of variation of 57.5% or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cellular product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of the cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have a maximum / minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10.In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface, and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface, and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have pore major axis / minor axis ratios of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have pore major axis / minor axis ratios of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10.In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less, and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less, and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less, and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less, and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and pore major axis / minor axis values ​​of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less, and maximum / minimum values ​​of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and pore major axis / minor axis values ​​of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less, and maximum / minimum values ​​of the average pore size in the membrane thickness direction of 1 to 10.In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore diameter with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface, and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface, and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the method for suppressing a decrease in membrane permeability of a cell product, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface, and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10.

[0181]

[174] The method for suppressing a decrease in membrane permeability of a cell product according to

[173] , wherein the porous membrane is a hollow fiber membrane.

[0182]

[175] A method for suppressing a decrease in membrane permeability of a cell product according to

[174] , wherein the hollow fiber membrane has a substantially uniform structure from the primary side to the secondary side in the membrane thickness direction.

[0183]

[176] A method for suppressing a decrease in membrane permeability of a cell product according to

[174] or

[175] , wherein the blocking pore size of the pores in the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

[0184]

[177] A method for suppressing a decrease in membrane permeability of a cell product according to any one of

[174] to

[176] , wherein the hollow fiber membrane is made of a synthetic polymer membrane.

[0185]

[178] The method for suppressing a decrease in membrane permeability of a cell product according to

[177] , wherein the synthetic polymer is polyvinylidene fluoride.

[0186]

[179] The method for suppressing a decrease in membrane permeability of a cell product according to any one of

[174] to

[178] , wherein the culture medium not filtered through the hollow fiber membrane is returned to the cell culture vessel.

[0187]

[180] A method for suppressing a decrease in membrane permeability of a cell product according to any one of

[173] to

[179] , wherein the product is an antibody.

[0188]

[181] The method for suppressing a decrease in membrane permeability of a cell product according to any one of

[173] to

[180] , wherein the cells are cultured by perfusion.

[0189]

[182] A cell culture vessel for culturing cells, a porous membrane for filtering a cell culture solution to obtain a cell product, and a pump for sending the culture solution from the culture vessel to the porous membrane, wherein the liquid-contacting surface of the porous membrane has at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane has at least one selected from the group consisting of an average pore size of 10 μm or less on the liquid-contacting surface, and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10, and the density of cells contained in the culture solution to be filtered is 8×10 ７A cell product production system having a cell density of 1000 cells / mL or more. In the cell product production system, the liquid-contacting surface may have an opening ratio of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product production system, the liquid-contacting surface may have a pore size / fiber diameter ratio of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface. In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface.In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface.In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product production system, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size of 1.3 or less, a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface.In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface.In the cell product production system, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid-contacting surface.In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid-contacting surface. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter / fiber diameter of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid-contacting surface. In the cell product production system, the liquid-contacting surface may have a pore diameter with a coefficient of variation of 0.5 or less, and a pore diameter / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid-contacting surface. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface.In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the cell product manufacturing system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.In the cell product production system, the liquid-contacting surface may have a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a degree of structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a degree of structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a degree of structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have pore major axis / minor axis ratios of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have pore major axis / minor axis ratios of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.In the cell product production system, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, the liquid-contacting surface may have pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have a pore diameter with an opening rate of 57.5% or less and a pore diameter with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, the liquid-contacting surface may have pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.In the cell product production system, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore diameter with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore diameter / fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have a pore diameter with a coefficient of variation of 0.5 or less, and a pore diameter / fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have pore major axis / minor axis ratios of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have pore sizes with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have pore major axis / minor axis ratios of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid-contacting surface and a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less and a pore diameter with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid-contacting surface and a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and maximum / minimum values ​​of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and maximum / minimum values ​​of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.In the cell product production system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product production system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.

[0190]

[183] ​​The system for producing a cell product according to

[182] , wherein the porous membrane is a hollow fiber membrane.

[0191]

[184] A cell product manufacturing system according to

[183] , wherein the hollow fiber membrane has a substantially uniform structure in the membrane thickness direction from the primary side to the secondary side.

[0192]

[185] A cell product manufacturing system according to

[183] ​​or

[184] , wherein the blocking pore size of the pores in the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

[0193]

[186] A cell product production system according to any one of

[183] ​​to

[185] , wherein the hollow fiber membrane is made of a synthetic polymer membrane.

[0194]

[187] The system for producing a cell product according to

[186] , wherein the synthetic polymer is polyvinylidene fluoride.

[0195]

[188] A cell product manufacturing system according to any one of

[182] to

[187] , further comprising a control unit that accepts input of data on the viscosity of the culture medium.

[0196]

[189] A cell product manufacturing system according to any one of

[182] to

[188] , further comprising a flow path for returning the culture solution that has not been filtered through the hollow fiber membrane to the culture tank.

[0197]

[190] A system for producing a cell product according to any one of

[182] to

[189] , wherein the product is an antibody.

[0198]

[191] The cell product production system according to any one of

[182] to

[190] , wherein the culture vessel cultures cells by perfusion.

[0199]

[192] A cell culture vessel for culturing cells, a porous membrane for filtering a cell culture solution to purify a product of the cells, and a pump for sending the culture solution from the culture vessel to the porous membrane, wherein the liquid-contacting surface of the porous membrane has at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane has at least one selected from the group consisting of an average pore size of 10 μm or less on the liquid-contacting surface, and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10, and the density of cells contained in the culture solution to be filtered is 8×10 ７A cell product purification system having a cell density of 1000000000000000 cells / mL or more. In the cell product purification system, the liquid-contacting surface may have an opening ratio of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product purification system, the liquid-contacting surface may have a pore size / fiber diameter ratio of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less.In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less.In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product purification system, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface.In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface.In the cell product purification system, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid-contacting surface.In the cell product purification system, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid-contacting surface. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface.In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.In the cell product purification system, the liquid-contacting surface may have a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a degree of structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have an aperture ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a degree of structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have an aperture ratio of 57.5% or less, a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a degree of structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have pore major axis / minor axis values ​​of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have pore major axis / minor axis values ​​of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10.In the cell product purification system, the liquid-contacting surface may have a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have pore major axes / minor axes of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have a pore size with an opening rate of 57.5% or less and a coefficient of variation of 0.5 or less, the liquid-contacting surface may have pore major axes / minor axes of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have pore major axes / minor axes of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have an opening ratio of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.In the cell product purification system, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore size / fiber size of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, a structural anisotropy of 0.97 to 1.03, and a pore major axis / minor axis ratio of 1.8 or less, and the porous membrane may have a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.In the cell product purification system, the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have pore major axis / minor axis ratios of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have pore sizes with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have pore major axis / minor axis ratios of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have a pore diameter / fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore diameter with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore diameter in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 μm or less, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and maximum / minimum values ​​of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and maximum / minimum values ​​of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size / fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less at the liquid-contacting surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10.In the cell product purification system, the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10. In the cell product purification system, the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid-contacting surface, and a maximum / minimum value of the average pore size in the film thickness direction of 1 to 10.

[0200]

[193] The system for purifying a cell product according to

[192] , wherein the porous membrane is a hollow fiber membrane.

[0201]

[194] The system for purifying a cell product according to

[193] , wherein the hollow fiber membrane has a substantially uniform structure in the membrane thickness direction from the primary side to the secondary side.

[0202]

[195] The system for purifying a cell product according to

[193] or

[194] , wherein the blocking pore size of the pores in the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

[0203]

[196] The system for purifying a cell product according to any one of

[193] to

[195] , wherein the hollow fiber membrane is made of a synthetic polymer membrane.

[0204]

[197] The cell product purification system according to

[196] , wherein the synthetic polymer is polyvinylidene fluoride.

[0205]

[198] The system for purifying a cell product according to any one of

[192] to

[197] , further comprising a control unit that accepts input of data on the viscosity of the culture medium.

[0206]

[199] The system for purifying a cell product according to any one of

[192] to

[198] , further comprising a flow path for returning the culture solution that was not filtered through the hollow fiber membrane to the culture tank.

[0207]

[200] A system for purifying a cell product according to any one of

[192] to

[199] , wherein the product is an antibody.

[0208]

[201] A system for purifying a cell product according to any one of

[192] to

[200] , wherein the culture vessel cultures cells by perfusion.

[0209] According to the present invention, it is possible to provide a method for producing a cell product, a method for purifying a cell product, a method for suppressing a decrease in membrane permeability of a cell product, a system for producing a cell product, and a system for purifying a cell product, which can suppress a decrease in the permeability of a cell product through a porous membrane.

[0210] FIG. 1 is a diagram schematically showing a cell product manufacturing system according to an embodiment. FIG. 2 is a diagram showing an example of image processing in the local thickness method according to an embodiment. FIG. 3 is a diagram showing an example of the largest circle shown in the local thickness method according to an embodiment. FIG. 4 is a diagram showing an example of image processing according to an embodiment. FIG. 5 is a diagram showing an example of image processing when calculating the structural anisotropy Z' of a porous membrane surface according to an embodiment. FIG. 6 is a diagram schematically showing the distribution of flow velocity and shear stress of a fluid flowing through a hollow portion when the porous membrane according to an embodiment is a hollow fiber membrane. FIG. 7 is a diagram schematically showing a cake layer and blockage in a cross section when the porous membrane according to an embodiment is a hollow fiber membrane. ２ 1 is a graph showing the relationship between the shear stress at the liquid-contacting surface of the hollow fiber membrane according to the example and the filtration rate of 300 L / m ２ 1 is a graph showing the relationship between the shear stress at the liquid-contacting surface of the hollow fiber membrane according to the example and the filtration rate of 300 L / m ２ 1 is a graph showing the relationship between the shear stress at the liquid-contacting surface of the hollow fiber membrane according to the example and the filtration rate of 300 L / m ２ 1 is a graph showing the relationship between the shear stress at the liquid-contacting surface of the hollow fiber membrane according to the example and the filtration rate of 300 L / m ２1 is a graph showing the relationship between the shear stress at the liquid-contacting surface of the hollow fiber membrane according to the example and the filtration rate of 300 L / m ２ 1 is a graph showing the relationship between the transmembrane pressure and the time point.

[0211] Hereinafter, an embodiment for carrying out the present invention (hereinafter referred to as "the present embodiment") will be described in detail. Note that the present embodiment is intended to facilitate understanding of the present invention and is not intended to limit the present invention. The present invention is not limited to the present embodiment, and can be carried out in various modifications within the scope of the gist thereof.

[0212] Referring to FIG. 1 , the method for producing a cell product according to this embodiment includes filtering a cell culture solution through a porous membrane 112 to obtain a cell product. For example, the cell culture solution is sent from a culture tank 111 to the porous membrane 112. The culture tank 111 may have a vent or filter with a pore size of 0.2 μm or less to prevent external bacteria from entering the culture tank 111. The culture tank 111 may be provided with an agitator 212 for agitating the culture solution in the culture tank 111. Cells are cultured in suspension in the culture solution in the culture tank 111.

[0213] The cells cultured in the culture tank 111 are not particularly limited. The cells may be derived from animals, including humans, or from microorganisms. The cells may be eukaryotic or prokaryotic. Examples of animals include mammals, reptiles, birds, amphibians, fish, and insects. The cells may be genetically modified cells. Examples of cells include CHO (Chinese Hamster Ovary) cells, HEK cells, BHK-21 cells, Sp2 / 0 cells, SP2 / 0-Ag14 cells, NS0 cells, Vero cells, PER.C6 cells, yeast, Bacillus subtilis, and Escherichia coli.

[0214] The cells may, for example, produce and release into the culture medium a pharmaceutically usable product. Examples of pharmaceutically usable products include peptides, proteins, and viruses (including virus-like particles). Examples of proteins include antibodies, hormones, cytokines, growth factors, enzymes, and plasma proteins. The protein may be a recombinant protein.

[0215] The antibody may be a monoclonal antibody or a polyclonal antibody. The antibody may be a human antibody or an antibody protein derived from a non-human mammal, such as a bovine or a mouse. Alternatively, the antibody may be a chimeric antibody protein with human IgG, or a humanized antibody. A chimeric antibody with human IgG is an antibody in which the variable region is derived from a non-human organism, such as a mouse, but the other constant regions are substituted with immunoglobulins derived from humans. A humanized antibody is an antibody in which the complementarity-determining region (CDR) of the variable region is derived from a non-human organism, but the other framework region (FR) is derived from humans. Humanization further reduces immunogenicity compared to chimeric antibodies.

[0216] By filtering a cell-containing culture solution using the porous membrane 112, the cells are removed from the culture solution, and the cell products in the culture solution permeate the porous membrane 112 and are purified. The surface of the porous membrane 112 that comes into contact with the culture solution to be filtered is called the liquid-contacting surface. The shape of the porous membrane 112 is not particularly limited. Examples of porous membranes include hollow fiber membranes, flat membranes, and tubular membranes. Below, an example will be described in which the porous membrane 112 is a hollow fiber membrane. In a hollow fiber membrane, the liquid-contacting surface to which the cell culture solution is supplied is called the primary side of the hollow fiber membrane. Furthermore, the surface from which the permeated solution that has permeated the hollow fiber membrane flows out is called the secondary side of the hollow fiber membrane. In an embodiment in which the cell culture solution to be filtered is supplied to the inner circumferential surface, the inner circumferential surface of the hollow fiber membrane is called the primary side, and the outer circumferential surface of the hollow fiber membrane is called the secondary side. In an embodiment in which the cell culture solution to be filtered is supplied to the outer circumferential surface, the outer circumferential surface of the hollow fiber membrane is called the primary side, and the inner circumferential surface of the hollow fiber membrane is called the secondary side.

[0217] The filtration method in the porous membrane 112 may be tangential flow filtration (TFF). Tangential flow filtration is a filtration method in which a culture solution is flowed in a direction parallel to the primary surface of the hollow fiber membrane on the primary surface of the hollow fiber membrane. Tangential flow filtration includes alternating tangential flow filtration (ATF). In this embodiment, the term "tangential flow filtration (TFF)" may refer to a filtration method in which a culture solution is flowed in one direction on the primary surface of the hollow fiber membrane. Alternating tangential flow filtration (ATF) refers to a filtration method in which a culture solution is flowed back and forth on the primary surface of the hollow fiber membrane.

[0218] Between the culture tank 111 and the porous membrane 112, there are arranged a flow path 113 for sending the culture solution in the culture tank 111 to the porous membrane 112, and a flow path 114 for returning the culture solution that has passed through the hollow portion of the porous membrane 112 without passing through the pores and passed through the porous membrane 112 without being filtered by the porous membrane 112 to the culture tank 111. The culture solution flowing through the flow path 113 may contain cells and cell products. The culture solution flowing through the flow path 114 without being filtered by the porous membrane 112 may contain cells and cell products. In addition, a flow path 115 is connected to the porous membrane 112 for collecting the culture solution that has passed through the pores of the porous membrane 112 and been filtered. The culture solution flowing through the flow path 115 and filtered by the porous membrane 112 may contain cell products. The culture solution filtered by the porous membrane 112 is collected, for example, in a container 201. The container 201 may be aseptically connected to the flow path 115. The flow channel 115 through which the culture medium filtered through the porous membrane 112 flows may be directly connected to, for example, a column used for the next purification step.

[0219] The flow path 113 is provided with, for example, a pump 123 for sending the culture solution in the culture tank 111 to the porous membrane 112. Examples of the pump include, but are not limited to, a diaphragm pump, a tube pump, a centrifugal pump, and a rotary pump. The flow path 113 may be provided with a pressure gauge 133 for measuring the pressure of the culture solution supplied to the porous membrane 112. The flow path 113 may be provided with a flow meter for measuring at least one of the flow rate and flow rate of the culture solution flowing through the flow path 113. The flow path 113 may be provided with a thermometer for measuring the temperature of the culture solution flowing through the flow path 113. The flow path 113 may be provided with a sampling unit for sampling the culture solution flowing through the flow path 113. The sampling unit is closed except during sampling.

[0220] The flow path 114 may be provided with a pump for sending the culture solution that has passed through the hollow portion without passing through the pores of the porous membrane 112 and has not been filtered by the porous membrane 112 to the culture tank 111. Note that pumps may be provided in both the flow path 113 and the flow path 114, or in either one. The flow path 114 may be provided with a pressure gauge 134 that measures the pressure of the culture solution that has passed through the porous membrane 112. The flow path 114 may be provided with a flow meter that measures at least one of the flow rate and flow rate of the culture solution flowing through the flow path 114. The flow path 114 may be provided with a thermometer that measures the temperature of the culture solution flowing through the flow path 114. The flow path 114 may be provided with a sampling unit for sampling the culture solution flowing through the flow path 114. The sampling unit is closed except during sampling.

[0221] The flow path 115 is provided with, for example, a pump 125 for sending the culture solution filtered by the porous membrane 112 through the pores of the porous membrane 112. The flow path 115 may be provided with a pressure gauge 135 for measuring the pressure of the culture solution filtered by the porous membrane 112. The flow path 115 may be provided with a flow meter for measuring at least one of the flow velocity and flow rate of the culture solution flowing through the flow path 115. The flow path 115 may be provided with a sampling unit for sampling the culture solution flowing through the flow path 115. The sampling unit is closed except when sampling is being performed.

[0222] The culture vessel 111 and the porous membrane 112 form at least a part of a path through which the culture medium circulates. The flow paths 113 and 114 also form at least a part of a path through which the culture medium circulates.

[0223] A flow path 116 for supplying a culture solution to the culture tank 111 may be connected to the culture tank 111. The flow path 116 is connected to, for example, a culture solution tank 216 that stores the culture solution. The flow path 116 is provided with, for example, a pump 126 for sending the culture solution to the culture tank 111. For example, the pumps 125 and 126 are controlled so that the amount of culture solution that is filtered through the porous membrane 112 and does not return to the culture tank 111 is the same as the amount of culture solution supplied to the culture tank 111. This control may be performed by observing the liquid level using a liquid level sensor (level sensor) installed in the culture tank 111 so that the liquid level is kept constant, or by measuring the weight of the entire culture tank 111 containing the culture solution so that the weight is kept constant.

[0224] A flow path 117 for supplying air containing carbon dioxide to the culture tank 111 may be connected to the culture tank 111. The flow path 117 is connected to, for example, a container 217 that stores air containing carbon dioxide. In addition, a flow path 118 for supplying oxygen to the culture tank 111 may be connected to the culture tank 111. The flow path 118 is connected to, for example, a container 218 that stores oxygen.

[0225] A flow path 119 for discharging at least a portion of the cells in the culture tank 111 may be connected to the culture tank 111. For example, by discharging at least a portion of the cells in the culture tank 111 using the flow path 119, the cell density in the culture solution in the culture tank 111 is maintained constant. This prevents an increase in cell density, which could lead to a shortage of oxygen and culture solution components in the culture solution, or an increase in the concentration of impurities. Discharging at least a portion of the cells in the culture tank 111 is called bleeding. Note that sampling may be performed using the flow path 119 to analyze the culture solution in the culture tank 111, but sampling is distinguished from bleeding because it is not intended to adjust the cell density.

[0226] The culture tank 111 may be provided with at least one of a thermometer for measuring the temperature of the culture solution in the culture tank 111, a DO meter for measuring DO (dissolved oxygen), and a pH meter for measuring pH.

[0227] [Method for Identifying the Structure of Porous Membrane] The pore feature amount, aperture ratio, fiber diameter, and structural anisotropy in the liquid-contacting surface structure of a porous membrane can be identified by the following method.

[0228] [Method for Obtaining an Image of the Wetted Surface of a Porous Membrane] When the porous membrane is a hollow fiber membrane, a razor is used to cut the center of the hollow fiber membrane parallel to the fiber length to expose the inner surface, which is then fixed with carbon paste to the observation specimen stage of a scanning electron microscope (SEM). The prepared specimen is then osmium-coated using an osmium coater (HPC-30W, manufactured by Vacuum Device Co., Ltd.) with the applied voltage adjustment knob set to 4.5 and a discharge time of 3 seconds to prepare an observation specimen. The specimen is irradiated with an electron beam under the following conditions, and the viewing angle is adjusted so that the vertical direction of the image is parallel to the fiber length of the hollow fiber membrane. The contrast is adjusted using the automatic function in a field of view consisting only of the skeleton resin and pores. The imaging magnification is set to a magnification that can explain the inner surface pore size distribution, such that the largest pores in the vertical direction of the image are between 5 and 60, and the largest pores in the horizontal direction of the image are between 7 and 60. For example, the magnification of the inner surface of the hollow fiber membrane used in the first example of the porous membrane described below is 150x, the magnification of the inner surface of the hollow fiber membrane used in the second example of the porous membrane is 5kx, and the magnification of the inner surface of the hollow fiber membrane used in the third example of the porous membrane is 3kx. A backscattered electron image is obtained that is free of structural distortion and abnormal contrast due to charge-up, is composed of the inner surface resin skeleton and inner surface pores, and does not include the sample stage, carbon paste, or razor cut surface. Note that even if the porous membrane is a membrane other than a hollow fiber membrane, the liquid-contacting surface can be photographed in the same way.

[0229] (SEM device conditions) SEM: Scanning electron microscope SU7000 manufactured by Hitachi High-Tech Corporation Probe current: Normal Acceleration voltage: 1 kV Working distance: 6 mm Detector: MD detector (backscattered electron image) Image size: 960 vertical x 1280 horizontal pixels

[0230] For one type of hollow fiber membrane, three lots of hollow fiber membranes are used, and SEM images (total of nine or more) from three or more fields of view without overlapping are obtained for each lot.

[0231] [Opening rate C of the liquid-contacting surface of the porous membrane ０' calculation method] Labels (letters and scale bar portions) on the electron microscope image are trimmed off. After filtering this image with a median filter using a 5x5 square kernel, two non-zero thresholds are determined using the multi-Otsu method. The larger of these thresholds is used as the threshold, and the image is binarized with pixels below the threshold as black and other pixels as white. The brightness of white is 255, and the brightness of black is 0. The binarized image is subjected to a closing process once using a 2x2 square kernel to remove noise. The total number of pixels in the entire image is calculated for the first analysis target image obtained as A ０ , the number of pixels that are black is B ０ The aperture ratio C of one SEM image is calculated from the following formula (1): ０ (%) is calculated. ０ =B ０ ×100 / A ０ (1)

[0232] For one type of hollow fiber membrane, three lots of SEM images of three fields of view (total of nine images) or more were used to measure the aperture ratio C ０ These aperture ratios C ０ The numerical average value of the opening ratio C of the inner surface of the hollow fiber membrane ０ 'Let's say.

[0233] It has been known that using a membrane with a high pore size for filtration can suppress deterioration of permeability due to clogging (WO 2001 / 053213). However, after extensive research, the present inventors have confirmed that a porous membrane with a lower pore size exhibits better filtration performance when used for tangential flow filtration in perfusion culture. Without being bound by theory, this is thought to be because a lower pore size in tangential flow filtration in perfusion culture makes it less likely for substances that cause membrane blockage to penetrate from the primary side into the membrane, and therefore the substances that cause membrane blockage are retained on the primary side. Therefore, a lower pore size on the liquid-contacting surface tends to make it less likely for membrane pores to become clogged due to the accumulation of removed substances on the membrane surface.

[0234] [Method for calculating fiber diameter F' of liquid-contacting surface of porous membrane] The first analysis object image is analyzed using the filters.local_thickness function of the porespy (2.0.2) library of python (3.7.10) described in Reference 1 (Gostick et al., (2019). PoreSpy: A Python Toolkit for Quantitative Analysis of Porous Media Images. Journal of Open Source Software, 4 (37), 1296.), with the first argument being the first analysis object image and the second argument being mode = 'dt'. filter. The local_thickness function is a function that analyzes white pixels in the first analysis target image, so when the first analysis target image is analyzed, the fiber diameter (unit: pixel), which is the diameter of the resin skeleton, is calculated. The diameter (unit: pixel) is multiplied by the pixel resolution (unit: m / pixel) to obtain the diameter (unit: m). The total number of white pixels D ０ , the sum of all the obtained diameters E ０ Using this, the fiber diameter F in one SEM image can be expressed by the following formula (2): F = E ０ / D ０ (2)

[0235] Since a diameter is assigned to each pixel, F is a weighted average of the fiber diameters in the SEM image. For one type of hollow fiber membrane, the fiber diameter F is calculated using SEM images of at least three fields of view (a total of nine images) from three lots. The number average of the fiber diameters F in all these SEM images is defined as the fiber diameter F' on the inner surface of the hollow fiber membrane.

[0236] Here, in the local thickness method used in the filters.local_thickness function, as shown in Figure 2, the diameter is calculated by filling in the circles that fit into the area surrounded by the contour, starting from the largest. Therefore, as shown in Figure 3, the area surrounded by the contour 500 into which the circle 501 can be placed does not have to be a circle. Also, as shown in Figure 4, the area surrounded by the contour 502 does not have to be a closed area completely surrounded by line segments. It is possible to calculate the effective diameter used in filtration for fibers and membrane pores on the surface of porous membranes of various shapes. The same applies to the method using the filters.local_thickness function described below.

[0237] [Method for calculating pore diameter I' on the liquid-contacting surface of a porous membrane] The first analysis target image is inverted to black and white, and a second analysis target image is obtained in which pixels that were white in the first analysis target image are turned black and pixels that were black in the first analysis target image are turned white. Using the filters.local_thickness function in the porespy (2.0.2) library of Python (3.7.10) described in Reference 1, analysis is performed with the first argument being the second analysis target image and the second argument being mode = 'dt'. Since the filter.local_thickness function is a function that analyzes white pixels in the second analysis target image, when the second analysis target image is analyzed, the pore diameter (unit: pixel) is calculated. The diameter (unit: pixel) is multiplied by the pixel resolution (unit: m / pixel) to obtain the diameter (unit: m). Using the total number of white pixels G and the sum of all the diameters obtained H, the pore diameter I in one SEM image can be expressed by the following formula (3). Since a diameter is assigned to each pixel, the pore diameter I is the weighted average of the pore diameters in the SEM image. I = H / G (3)

[0238] For one type of hollow fiber membrane, SEM images of at least three fields of view for each of three lots (a total of nine images) are used to calculate the pore diameter I. The number average value of the pore diameters I of all these SEM images is defined as the pore diameter I' of the inner surface of the hollow fiber membrane.

[0239] [Method for calculating the coefficient of variation V of pore diameters on the liquid-contacting surface of a porous membrane] When the standard deviation of the pore diameters I in all the SEM images is S, the coefficient of variation V of the pore diameters I is given by the following formula (4): V=S / I′ (4)

[0240] A large coefficient of variation in pore size means a large variation in pore size. In a cell culture solution containing impurities of various sizes and states, large variations in pore size are thought to make it easier for the impurities to become trapped on the porous membrane surface and serve as a foothold for the accumulation of impurities on the porous membrane surface. Therefore, a smaller coefficient of variation in pore size on the liquid-contacting surface tends to make it less likely for the membrane pores to become clogged due to the accumulation of removed substances on the membrane surface.

[0241] [Calculation of pore diameter / fiber diameter J′ at the liquid-contacting surface of the porous membrane] Using the pore diameter I and fiber diameter F in each SEM image, the pore diameter / fiber diameter ratio J is given by the following formula (5): J=I / F (5)

[0242] For one type of hollow fiber membrane, the pore size / fiber diameter ratio J is calculated using SEM images of at least three fields of view for each of three lots (a total of nine membranes). The number average value of the pore size / fiber diameter ratio J in all these SEM images is taken as the pore size / fiber diameter J' on the inner surface of the hollow fiber membrane. The ratio of the pore size to the fiber diameter on the liquid-contacting surface of the porous membrane (pore size / fiber diameter) is a value obtained by normalizing the effective pore size for filtration using the fiber diameter.

[0243] It is thought that the smaller the pore size normalized by the fiber diameter, the less likely it is that substances that cause membrane blockage will penetrate into the membrane from the primary side, and the substances that cause membrane blockage will be retained on the primary side. Therefore, the smaller the pore size / fiber diameter on the liquid-contacting surface, the less likely it is that membrane pores will be blocked by the accumulation of removed substances on the membrane surface.

[0244] [Calculation of the long diameter / short diameter M'' of pores present on the liquid-contacting surface of a porous membrane] Independent white regions are extracted from the second image to be analyzed. For each extracted white region, the contour of each region is detected by extracting white pixels whose adjacent pixels in either the up, down, left, or right direction are black. As shown in Figure 5, of the rectangles circumscribing this contour, taking rotation into consideration, the rectangle with the smallest area is determined as the circumscribing rectangle. Of the four sides of the circumscribing rectangle, the length of the short side is the short diameter K and the length of the long side is the long diameter L. If this is the case, M, which represents the long diameter / short diameter of a certain contour, is given by the following equation (6): M = L / K (6)

[0245] M (long diameter / short diameter) is calculated for all contours contained in one SEM image, and the number average value is defined as M'. M' is calculated using SEM images of at least three fields of view for each of three lots (a total of nine images) for one type of hollow fiber membrane. The number average value of M' in all these SEM images is defined as the average value M'' of the long diameter / short diameter of the pores present on the inner surface of the hollow fiber membrane. The ratio of the long diameter to the short diameter of the pores on the liquid-contacting surface of the porous membrane (long diameter / short diameter) is an index of the anisotropy of the pores on the liquid-contacting surface.

[0246] [Measurement of the structural anisotropy Z' of the liquid-contacting surface of the porous membrane] A 512 x 512 pixel analysis object image O having the upper left corner as one end in the first analysis object image is Ｉ and O with the bottom left vertex as one end Ｉ The analysis target image P of the same size as Ｉ , O with the upper right vertex as one end Ｉ and the same size as the analysis target image Q Ｉ , the bottom right vertex is one end Ｉ The analysis target image R of the same size as Ｉ The analysis target image O is extracted. Ｉ In contrast, O Ｉ A masking process is performed by blacking out the outside of a circle with a diameter of 512 pixels and centered on the third analysis object image for FFT analysis. After converting the third analysis object image into a brightness matrix, a two-dimensional fast Fourier transform is performed using the fft.fft2 function in the Numpy (1.20.3) library of Python (3.7.10), to obtain the matrix T Ｓ where the first argument of the fft.fft2 function is the third analysis target image, and the others are set to default settings. Then, the matrix TＳ The fft.fftshift function of Numpy (1.20.3) is used to rearrange the matrix T so that the low frequency components are at the center. However, the first argument of the fft.fftshift function is the matrix T Ｓ The rest of the settings are default. Then, the power spectrum U is obtained by the following equation (7): U=20×log(T) (7)

[0247] The obtained power spectrum U is transformed into a 360 × 360 matrix T with the center of the power spectrum as the origin by using the warpPolar function of the OpenCV (4.5.2) library of Python (3.7.10). Ｖ However, the horizontal direction of the image shown in FIG. 6 is set to 0° in polar coordinates, and polar coordinate transformation is performed in the θ direction. Then, the matrix T Ｖ matrix T representing the row-by-row intensity average of Ｗ We obtain the matrix T Ｗ is a one-column matrix that corresponds to the intensity average for each angle. The intensity average is a number average. Ｗ The matrix T is obtained by adding all the elements of Ｗ Get the element average of matrix T Ｗ Divide by the element mean and obtain matrix T Ｙ get.

[0248] Let n be any natural number and let T Ｙ The element in the nth row of Y ｎ When expressed as above, the average intensity X around 180° in the power spectrum is １８０ is given by the following equation (8): １８０ = (Y １７８ +Y １７９ +Y １８０ +Y １８１ +Y １８２ ) / 5 (8)

[0249] In addition, the average intensity X around 90° in the power spectrum ９０ is given by the following equation (9): ９０ = (Y ８８ +Y ８９ +Y ９０ +Y ９１ +Y ９２) / 5 (9)

[0250] Using these, the analysis target image O Ｉ Structural anisotropy Z Ｏ is given by the following equation (10): Ｏ =X ９０ / X １８０ (10)

[0251] In the same manner as above, the analysis object image P Ｉ , Q Ｉ , R Ｉ The structural anisotropy obtained by analyzing Z Ｐ , Z Ｑ , Z Ｒ Then, the structural anisotropy Z in one SEM image is given by the following formula (11): Z=(Z Ｏ +Z Ｐ +Z Ｑ +Z Ｒ ) / 4 (11)

[0252] For one type of hollow fiber membrane, the structural anisotropy Z is calculated using SEM images of at least three fields of view (a total of nine images) for each of three lots. The number average of the structural anisotropy Z in all these SEM images is taken as the structural anisotropy Z' of the liquid-contacting surface of the hollow fiber membrane. When the structural anisotropy Z' of the porous membrane surface is 1, this indicates that the pores are uniformly oriented in the vertical and horizontal directions of the image, and the anisotropy of the membrane structure is small. When the structural anisotropy Z' is greater than 1, this indicates that the membrane structure is oriented in the horizontal direction of the image. When the structural anisotropy Z' is less than 1, this indicates that the membrane structure is oriented in the vertical direction of the image.

[0253] [Method for calculating the maximum / minimum average pore diameter in the membrane thickness direction of a porous membrane] (Cross-section preparation) After fixing the hollow fiber membrane to a sample stage with carbon paste, a cross-section in the membrane thickness direction is prepared using an ion milling device E-3500 (manufactured by Hitachi High-Tech Corporation) under the following cross-section preparation conditions. The cross-section is a smooth cross-section in which an Ar ion beam penetrates from the outer surface to the inner surface of the hollow fiber membrane, the resin skeleton is not deformed by heat, and no sputtered sample pieces are attached. Note that even when the porous membrane is a membrane other than a hollow fiber membrane, a cross-section in the membrane thickness direction can be prepared in the same manner.

[0254] (Cross-section preparation conditions) Acceleration voltage: 3 kV Probe current: 20 μA

[0255] (Cross-Sectional SEM Observation) Using an osmium coater (HPC-30W, manufactured by Vacuum Device Co., Ltd.), a sample prepared under conditions of an applied voltage adjustment knob setting of 4.5 and a discharge time of 3 seconds was coated with osmium to prepare an observation sample. An electron beam was irradiated onto the observation sample under the observation conditions described below, and the contrast was adjusted using the automatic function in a field of view consisting only of the skeleton resin and pores. Furthermore, the imaging magnification was set to a value that would result in an average pore diameter of 10 to 20 pixels at the position where the average pore diameter was smallest in the cross section. For example, the cross-sectional imaging magnification for the first and second examples of porous membranes described below was 5kx, and the cross-sectional imaging magnification for the hollow fiber membrane used in the third example of porous membrane was 3kx. Under the above conditions, the outer surface was aligned with the right side of the SEM image, and a first backscattered electron image was obtained in which the hollow fiber membrane thickness direction and the lateral direction of the SEM image were parallel. Note that this backscattered electron image is an image focused on a smooth cross section and is free of structural distortion or abnormal contrast due to charge-up. When the porous membrane is a membrane other than a hollow fiber membrane, the cross section in the membrane thickness direction may be photographed in the same manner.

[0256] [Observation conditions] SEM: Hitachi High-Technologies Corporation, Scanning Electron Microscope SU7000 Probe current: Normal Acceleration voltage: 1 kV Working distance: 3 mm Detector: MD detector (backscattered electron image) Image size: 960 vertical x 1280 horizontal pixels

[0257] Next, the field of view of the first backscattered electron image is shifted parallel to the film thickness direction toward the inner surface, and a second backscattered electron image is obtained. However, the fields of view are slightly overlapped so that the hole structure in the second backscattered electron image smoothly connects with the hole structure in the first backscattered electron image. The process of acquiring backscattered electron images while shifting the field of view in the film thickness direction and slightly overlapping it with the previous field of view continues, and imaging is terminated when the inner surface is included in the backscattered electron image.

[0258] The labels (letters and scale bar) of the obtained backscattered electron images are trimmed away, and all images are combined so that the pore structure is smoothly connected, to obtain a single cross-sectional SEM image. However, since the cross-sectional images are rectangular, if there is any vertical misalignment in the SEM images when combined, this is removed by trimming after combination. Because the cross section of a hollow fiber membrane is essentially circular, the objective is to obtain a high-resolution cross section in an area that can be sufficiently approximated as a rectangle.

[0259] The cross-sectional SEM image is trimmed so that the left edge is the inner surface and the right edge is the outer surface, thereby obtaining a first cross-sectional SEM image. The first cross-sectional SEM image has the same pixel resolution as the first backscattered electron image. If the resin skeleton present in the depth direction of the pores is observed with a brightness brighter than the cross-sectional resin, the resin skeleton present in the depth direction may be hand-painted with a dark color so that it is recognized as part of the pores in the binarization process.

[0260] (Analysis of Cross-Sectional Pore Size) Cross-sectional pore size analysis is performed as follows. Within the first cross-sectional SEM image, a first region with a width of 100 pixels, including the leftmost edge, is extracted. The height of all extracted regions is assumed to be the same as that of the first cross-sectional SEM image. The maximum diameter, pore size variation coefficient, average pore size, and aperture ratio of the multiple pores contained in the first region are calculated. The first region is filtered using a median filter with a 5x5 square kernel, and then two non-zero thresholds are determined using the multi-Otsu method. The larger of these thresholds is used as the threshold, and the image is binarized, with pixels below the threshold being white and all other pixels being black. Note that the brightness of white is 255 and the brightness of black is 0. The binarized image is subjected to a closing process once using a 2x2 square kernel to remove noise. The resulting image to be analyzed is then passed through the filters.filter() function in the porespy (2.0.2) library of Python (3.7.10). The local_thickness function is used to perform analysis with the first argument being the image to be analyzed and the second argument being mode = 'dt'. Since the filters.local_thickness function is a function that performs analysis on white pixels in the image to be analyzed, the pore diameter (unit: pixel) is calculated. The pore diameter (unit: pixel) is multiplied by the pixel resolution (unit: m / pixel) to obtain the pore diameter (unit: m). The pore diameters are given for all pixels, and the largest of these is the maximum pore diameter I of the first region. ｍａｘ（１） Let's say.

[0261] The coefficient of variation of the pore size in the pore size distribution in the image to be analyzed is the coefficient of variation V １ Furthermore, the total number of white pixels D １ , the sum of the pore diameters given for all pixels E １ The average pore diameter I of the extracted area is calculated using １ is given by the following equation (12): １ = E １ / D １ (12) Also, the aperture ratio C １ (%) is the total number of pixels in the first area A １ is given by the following equation (13) using C １ =D １ ×100 / A１ (13)

[0262] Coefficient of variation of pore size in the first region V １ is within a predetermined range of greater than 0.3 and less than 0.5, the center of the 100-pixel width of the first region in the direction perpendicular to the left edge is taken as the center of the first region. １ is greater than the predetermined range, the pore size variation coefficient V １ The width W of the first region is set to within a predetermined range. １ is narrowed according to the following formula (14), and then the maximum pore diameter I ｍａｘ（１） , coefficient of variation V １ , average pore size I １ , aperture ratio C １ The width W of the first region is calculated. １ The center of N is the center of the first region. １ indicates the number of times the area is retaken until it falls within the specified range. １ = (10-0.1 x N １ ) × I ｍａｘ（１） (14)

[0263] Coefficient of variation of pore size V １ If is smaller than the predetermined range, the coefficient of variation of the pore size V １ The width W of the first region is set to within a predetermined range. １ is expanded according to formula (15), and then the maximum pore diameter I ｍａｘ（１） , coefficient of variation V １ , average pore size I １ , aperture ratio C １ The width W of the first region is calculated. １ The center of N is the center of the first region. １ indicates the number of times the area is retaken until it falls within the specified range. １ = (10 + 0.1 x N １ ) × I ｍａｘ（１） (15)

[0264] Coefficient of variation V １ satisfies the predetermined range, and the finally determined average pore diameter I １ , aperture ratio C １is recorded in correspondence with the center coordinates of the first region.

[0265] Hereinafter, n is an integer with an initial value of 0, and the center of the (n+2)th region is set to be 100 pixels away from the center of the (n+1)th region in the direction perpendicular to the left edge of the first cross-sectional SEM image. ｎ＋２ is the maximum value I of the pore diameter included in the n+1th region ｍａｘ（ｎ＋１） is determined by equation (16) using W ｎ＋２ = 10 × I ｍａｘ（ｎ＋１） (16)

[0266] The coefficient of variation of the maximum diameter and pore size of multiple contours contained in the n+2th region is calculated. The n+2th region is filtered using a median filter with a 5x5 square kernel, and then two non-zero thresholds are determined using the multi-Otsu method. The larger of these thresholds is used as the threshold, and the image is binarized, with pixels below the threshold being white and all other pixels being black. Note that the brightness of white is 255 and the brightness of black is 0. The binarized image is subjected to a closing process once using a 2x2 square kernel to remove noise. The resulting image to be analyzed is analyzed using the filters.local_thickness function in the porespy (2.0.2) library in Python (3.7.10), with the first argument being the image to be analyzed and the second argument being mode = 'dt'. Since the local_thickness function is a function that performs analysis on white pixels in the image to be analyzed, the pore diameter (unit: pixel) is calculated. The pore diameter (unit: pixel) is multiplied by the pixel resolution (unit: m / pixel) to obtain the pore diameter (unit: m). The pore diameter is given for all pixels, and the largest pore diameter among them is the maximum pore diameter I of the n+2th region. ｍａｘ（ｎ＋２） Let's say.

[0267] The coefficient of variation of the pore size in the pore size distribution in the image to be analyzed is V ｎ＋２ Furthermore, the total number of white pixels D ｎ＋２ , the sum of the pore diameters given for all pixels E ｎ＋２ Using this, the average pore diameter I of the n+2th region ｎ＋２is given by the following equation (17): ｎ＋２ = E ｎ＋２ / D ｎ＋２ (17)

[0268] In addition, the aperture ratio C ｎ＋２ (%) is the total number of white pixels D ｎ＋２ , the total number of pixels in the n+2th region A ｎ＋２ is given by the following equation (18) using C ｎ＋２ =D ｎ＋２ ×100 / A ｎ＋２ (18)

[0269] Coefficient of variation V of pore size in the n+2th region ｎ＋２ is within a predetermined range of greater than 0.3 and less than 0.5, the width W of the n+2th region in the direction perpendicular to the left edge ｎ＋２ Coefficient of variation of pore size V ｎ＋２ If is greater than the predetermined range, the diameter variation coefficient V ｎ＋２ The width W of the n+2th region is adjusted according to equation (19) until it falls within the predetermined range. ｎ＋２ After narrowing the diameter, the maximum hole diameter I ｍａｘ（ｎ＋２） , coefficient of variation V ｎ＋２ , average pore size I ｎ＋２ , aperture ratio C ｎ＋２ In equation (19), N ｎ＋２ indicates the number of times the area is retaken until it falls within the specified range. ｎ＋２ = (10-0.1 x N ｎ＋２ ) × I ｍａｘ（ｎ＋２） (19)

[0270] If the diameter variation coefficient is smaller than the predetermined range, the width W of the n+2th region is adjusted according to equation (20) while maintaining the center of the n+2th region until the diameter variation coefficient falls within the predetermined range. ｎ＋２ After widening the hole, set the maximum hole diameter I again. ｍａｘ（ｎ＋２） , coefficient of variation V ｎ＋２ , average pore size I ｎ＋２ , aperture ratio C ｎ＋２ In equation (20), N ｎ＋２ indicates the number of times the area is retaken until it falls within the specified range. ｎ＋２= (10 + 0.1 x N ｎ＋２ ) × I ｍａｘ（ｎ＋２） (20)

[0271] Coefficient of variation V ｎ＋２ satisfies the predetermined range, and the finally determined average pore diameter I ｎ＋２ , aperture ratio C ｎ＋２ is recorded in correspondence with the center coordinates of the n+2th region.

[0272] Thereafter, n is incremented by 1 to obtain the average pore diameter I of the n+1th region. ｎ＋１ , and aperture ratio C ｎ＋１ This calculation is repeated until the center of the n+2th region exceeds the right edge of the first cross-sectional SEM image. ｎ＋１ Among these, the corresponding aperture ratio C ｎ＋１ The exception is that the average pore diameter I ｎ＋１ When the graph in which the average pore diameter I is plotted against the coordinates of the center of the region is compared with the first cross-sectional SEM image, if the value is clearly unnatural, that point is deleted. ｎ＋１ Among these, the maximum value of the average pore diameter in the membrane thickness direction is I ｍａｘ , the minimum value of the average pore diameter in the film thickness direction is I ｍｉｎ R, which is the ratio (maximum value / minimum value) of the maximum value to the minimum value of the average pore diameter from the primary side surface to the secondary side surface in the thickness direction of the porous membrane, is given by the following equation (21): R=I ｍａｘ / I ｍｉｎ (21)

[0273] R is calculated for three or more lots of one type of hollow fiber membrane, and the number average value is taken as the maximum / minimum value R' of the average pore diameter in the membrane thickness direction of the porous membrane.

[0274] The greater the ratio R' of the maximum average pore size to the minimum average pore size, the greater the variation in the pore size in the film thickness direction of the porous membrane. The closer the ratio R' of the maximum average pore size to the minimum average pore size, the less variation in the pore size in the film thickness direction of the porous membrane.

[0275] The maximum / minimum value R' of the average pore size in the thickness direction of the porous membrane reflects the variation in the pore size in the thickness direction of the porous membrane, and therefore is closely correlated with the mechanism of progression of membrane clogging inside the porous membrane. Therefore, without being bound by theory, it is believed that there is an appropriate combination between the structural characteristics of the liquid-contacting surface of the porous membrane and the filtration conditions to exhibit excellent filtration performance.

[0276] [Blocking pore size of porous membrane] The blocking pore size is exemplified as the particle size of particles at which the permeation rejection rate of the particles is 90% when a particle dispersion containing particles of a certain particle size is filtered using a porous hollow fiber membrane. It is also referred to as the minimum pore size. To determine the blocking pore size, polystyrene latex particles (manufactured by JSR Corporation, SIZE STANDARD PARTICLES) are dispersed in a 0.5% by mass aqueous solution of sodium dodecyl sulfate (manufactured by Wako Pure Chemical Industries, Ltd.) to a particle concentration of 0.01% by mass to prepare a latex particle dispersion. The latex particle dispersion is filtered using a porous hollow fiber membrane, and the change in latex particle concentration before and after filtration is measured. This measurement is performed while changing the latex particle size, and a blocking curve for the latex particles is created. From this blocking curve, the particle size that allows 90% permeation rejection is read, and this diameter is used as the blocking pore size.

[0277] [Membrane Thickness of Porous Membrane] The inner diameter (μm) and outer diameter (μm) of the hollow fiber membrane can be measured by cutting the hollow fiber membrane into a thin cylindrical shape and observing the slice under an optical microscope (Keyence Corporation, VHX-7000). Ｉ and outer diameter W Ｏ From the above, the membrane thickness W of the hollow fiber membrane is calculated using the following formula (22): ＴＨ (μm) can be calculated. ＴＨ = (W Ｏ -W Ｉ ) / 2 (22)

[0278] [Shear Stress] The shear stress SS due to the flow of the culture solution on the liquid-contacting surface of the porous membrane is given by the product of the viscosity VC (Pa s) of the culture solution flowing through the hollow part of the hollow fiber membrane and the shear rate SV ( / s), as shown in the following formula (23): SS = VC × SV (23)

[0279] The viscosity of the culture medium can be affected by, for example, the temperature of the culture medium, the composition of the culture medium, and the density of cells in the culture medium. In particular, anti-foaming polymers that may be contained in the culture medium can affect the viscosity of the culture medium.

[0280] Without being bound by theory, under laminar flow conditions of a Newtonian fluid, the flow of the culture solution in the hollow part of the hollow fiber membrane is a Hagen-Poiseuille flow, and as shown in Figure 7, the distribution of the flow velocity of the culture solution in the hollow part of the hollow fiber membrane is a quadratic curve with the center of the hollow part of the hollow fiber membrane as the axis. The shear rate of the culture solution is the slope of this quadratic curve. The shear rate SV of the culture solution reaches a maximum SVmax at the liquid-contacting surface of the hollow fiber membrane, LV is the linear velocity of the culture solution (m / s), W is the linear velocity of the culture solution (m / s), and W is the shear rate of the culture solution (m / s). Ｉ is the inner diameter (m) of the hollow fiber membrane, the shear stress is given by the following formula (24). As shown in Figure 7, the shear stress also reaches a maximum SSmax at the liquid-contacting surface of the hollow fiber membrane. SVmax = 8LV / W Ｉ (24)

[0281] In this embodiment, even if the flow of the culture solution is not a laminar flow condition of a Newtonian fluid, but is, for example, a turbulent flow, the shear stress can be calculated from the above formula (23).

[0282] When a culture medium containing cells flows through the hollow portion of a hollow fiber membrane, a density polarization layer with a high cell density is formed on the inner surface (primary surface) of the hollow fiber membrane, as shown in Figure 8. Furthermore, cells accumulate on the inner surface (primary surface) of the hollow fiber membrane, forming a cake layer. The density polarization layer and cake layer cause a decrease in the permeability of cell products without a decrease in the flow rate of the permeate through the hollow fiber membrane. Furthermore, if substances contained in the culture medium clog the inside of the hollow fiber membrane, the flow rate of the permeate through the hollow fiber membrane decreases and the permeability of the cell products decreases. Because cell products such as antibodies are very expensive, even a slight decrease in permeability can have a significant impact on the cost of biopharmaceuticals.

[0283] [Permeability through porous membrane] The permeability P (%) of the cell product is given by the following formula (25), where Q1 is the concentration of the cell product in the culture medium before filtration through the porous membrane, and Q2 is the concentration of the cell product in the culture medium after filtration through the porous membrane. P = Q2 × 100 / Q1 (25)

[0284] [Transmembrane pressure difference in porous membrane] Blockage inside the hollow fiber membrane can be evaluated by the transmembrane pressure difference. If the pressure of the culture solution supplied to the primary side of the hollow fiber membrane is O1i, the pressure of the culture solution that passes through the primary side of the hollow fiber membrane without being filtered by the hollow fiber membrane is O1o, and the pressure of the culture solution that is filtered by the hollow fiber membrane and discharged from the secondary side is O2, the transmembrane pressure difference Om in the hollow fiber membrane is given by the following formula (26): Om = (O1i + O1o) / 2 - O2 (26) The higher the degree of blockage inside the hollow fiber membrane, the higher the transmembrane pressure difference.

[0285] [First Example of Porous Membrane] In the first example of the porous membrane, the aperture ratio at the liquid-contacting surface is, for example, 57.5% or less, 55% or less, or 52.5% or less. The aperture ratio is, for example, 1% or more, 5% or more, or 10% or more. The aperture ratio is, for example, 1% or more and 57.5% or less, 5% or more and 57.5% or less, 10% or more and 57.5% or less, 1% or more and 55% or less, 5% or more and 55% or less, 10% or more and 55% or less, 1% or more and 52.5% or less, 5% or more and 52.5% or less, or 10% or more and 52.5% or less. In the first example of the porous membrane, a smaller aperture ratio tends to reduce the likelihood of clogging of the membrane pores due to the accumulation of removed material on the membrane surface.

[0286] In the first example of the porous membrane, the structural anisotropy of the liquid-contacting surface is, for example, 0.97 or more, 0.975 or more, 0.98 or more, 0.985 or more, or 0.99 or more. The structural anisotropy of the liquid-contacting surface is, for example, 1.03 or less, 1.025 or less, 1.02 or less, 1.015 or less, or 1.01 or less. The structural anisotropy of the liquid-contacting surface is, for example, 0.97 or more and 1.03 or less, 0.975 or more and 1.025 or less, 0.98 or more and 1.02 or less, 0.985 or more and 1.015 or less, or 0.99 or more and 1.01 or less. In the first example of the porous membrane, the smaller the anisotropy of the liquid-contacting surface, the less likely clogging of membrane pores due to the accumulation of removed matter on the membrane surface tends to occur.

[0287] In the first example of the porous membrane, the ratio of the major axis to the minor axis of the pores at the liquid-contacting surface is, for example, 1 or more, or 1.05 or more. The ratio of the major axis to the minor axis of the pores is, for example, 1.8 or less, 1.75 or less, 1.7 or less, or 1.65 or less. The ratio of the major axis to the minor axis of the pores is, for example, 1 or more and 1.8 or less, 1 or more and 1.75 or less, 1 or more and 1.7 or less, 1 or more and 1.65 or less, or 1.05 or more and 1.65 or less. In the first example of the porous membrane, the smaller the anisotropy of the pores at the liquid-contacting surface, the less likely the membrane pores are to be clogged by the accumulation of removed matter on the membrane surface.

[0288] In the first example of the porous membrane, the pore size / fiber size at the liquid-contacting surface is, for example, 0.05 or more, 0.1 or more, 0.2 or more, 0.3 or more, 0.4 or more, or 0.5 or more. The pore size / fiber size at the liquid-contacting surface is, for example, 1.3 or less, 1.25 or less, 1.2 or less, 1.15 or less, or 1.1 or less. The pore size / fiber size at the liquid-contacting surface is, for example, 0.05 or more and 1.3 or less, 0.1 or more and 1.3 or less, 0.2 or more and 1.3 or less, 0.3 or more and 1.3 or less, 0.4 or more and 1.25 or less, 0.4 or more and 1.2 or less, or 0.5 or more and 1.1 or less. In the first example of the porous membrane, the smaller the pore size / fiber size, the less likely clogging of the membrane pores due to the accumulation of removed matter on the membrane surface tends to occur.

[0289] In the first example of the porous membrane, the coefficient of variation of the pore size at the liquid-contacting surface is 0 or more, 0.01 or more, 0.03 or more, or 0.05 or more. The coefficient of variation of the pore size is 0.5 or less, 0.49 or less, 0.48 or less, or 0.47 or less. The coefficient of variation of the pore size is 0 or more and 0.5 or less, 0.01 or more and 0.5 or less, 0.03 or more and 0.5 or less, 0.05 or more and 0.5 or less, 0.01 or more and 0.49 or less, 0.03 or more and 0.48 or less, or 0.05 or more and 0.47 or less. In the first example of the porous membrane, the smaller the variation of the pore size at the liquid-contacting surface, the less likely the membrane pores are to be clogged due to the accumulation of removed matter on the membrane surface.

[0290] In the first example of the porous membrane, the ratio of the maximum value to the minimum value (maximum value / minimum value) when calculating the average pore diameter of the portion of the porous membrane at the same distance from the membrane surface in the film thickness direction is 3 or more, 5 or more, or 10 or more. The maximum value / minimum value of the average pore diameter is 1000 or less, 500 or less, or 100 or less. The maximum value / minimum value of the average pore diameter is 3 or more and 1000 or less, 5 or more and 1000 or less, 10 or more and 1000 or less, 3 or more and 500 or less, 5 or more and 500 or less, 10 or more and 500 or less, 3 or more and 100 or less, 5 or more and 100 or less, or 10 or more and 100 or less. The greater the maximum value / minimum value of the average pore diameter is from 1, the more the pore diameter of the porous membrane varies in the film thickness direction.

[0291] In the first example of the porous membrane, the porous membrane may be a hollow fiber membrane. The porous structure of the hollow fiber membrane may have a gradient structure in which the average pore size decreases from the primary side to the secondary side in the membrane thickness direction. In a hollow fiber membrane with a gradient structure, the average pore size on the primary surface is larger than the average pore size on the secondary surface, and the pore size decreases from the primary surface toward the minimum pore size layer. Note that there may be a portion between the primary surface and the secondary surface where the pore size does not change. In a hollow fiber membrane with a gradient structure, the pore size distribution is asymmetric in the membrane thickness direction. A layer with a relatively large pore size near the primary surface of the hollow fiber membrane is called a coarse layer. A layer with a relatively small pore size near the secondary surface of the hollow fiber membrane is called a dense layer. The minimum pore size layer, where the pore size is smallest, is included in the dense layer.

[0292] In the first example of the porous membrane, the average pore size of the primary surface of the hollow fiber membrane having a gradient structure is, for example, 1 μm or more, 5 μm or more, 10 μm or more, or 15 μm or more. The average pore size of the primary surface is, for example, 140 μm or less, 120 μm or less, 100 μm or less, or 80 μm ...

Claims

1. filtering a culture medium of the cells through a porous membrane to obtain a product of the cells; The porous membrane has a liquid-contacting surface having at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less; and The liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis ratio of 1.8 or less; and The shear stress due to the flow of the culture medium on the liquid-contacting surface is 4.0 N / m 2 To the following, Methods for producing cell products.

2. The method for producing a cell product described in claim 1, wherein the porous membrane has at least one selected from the group consisting of an average pore size of 1 μm or more at the liquid-contacting surface and a maximum / minimum value of the average pore size in three or more thickness directions.

3. The method for producing a cell product described in claim 1, wherein the porous membrane has at least one selected from the group consisting of an average pore size of 10 μm or less at the liquid contact surface, and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10.

4. The method for producing a cell product according to claim 2 , wherein the porous membrane is a hollow fiber membrane.

5. The method for producing a cell product according to claim 4 , wherein the hollow fiber membrane has a gradient structure in which the average pore size decreases in the membrane thickness direction from the primary side to the secondary side.

6. The method for producing a cell product according to claim 4, wherein the pores of the hollow fiber membrane have a blocking pore size of 0.05 μm or more and 20 μm or less.

7. The method for producing a cell product according to claim 4 , wherein the hollow fiber membrane is made of a synthetic polymer membrane.

8. The method for producing a cell product according to claim 7, wherein the synthetic polymer is polysulfone.

9. The method for producing a cell product according to claim 4 , wherein the hollow fiber membrane has a coarse layer and a dense layer.

10. The method for producing a cell product according to claim 3 , wherein the porous membrane is a hollow fiber membrane.

11. The method for producing a cell product according to claim 10, wherein the hollow fiber membrane has a substantially uniform structure in the membrane thickness direction from the primary side to the secondary side.

12. The method for producing a cell product according to claim 10, wherein the pore size of the pores in the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

13. The method for producing a cell product according to claim 10, wherein the hollow fiber membrane is made of a synthetic polymer membrane.

14. The method for producing a cell product according to claim 13, wherein the synthetic polymer is polyvinylidene fluoride.

15. The shear stress is measured based on the viscosity of the culture medium, and the measured shear stress is 4.0 N / m 2 The method for producing a cell product according to claim 1 , further comprising controlling a flow rate of the culture solution filtered through the porous membrane in a direction parallel to the membrane surface so as to be as follows:

16. The method for producing a cell product according to claim 1 , wherein the culture medium that is not filtered through the porous membrane is returned to the cell culture vessel.

17. The method of claim 1 , wherein the product is an antibody.

18. The method of claim 1 , wherein the cells are in perfusion culture.

19. The density of the cells contained in the culture medium is 8×10 7 The method for producing a cell product according to claim 3, wherein the concentration of the cell product is 100 μg / mL or more.

20. filtering a culture medium of the cells through a porous membrane to obtain a product of the cells; The porous membrane has a liquid-contacting surface having at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less; and The liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 or less and a pore major axis / minor axis ratio of 1.8 or more; and The shear stress due to the flow of the culture medium on the liquid-contacting surface is 4.0 N / m 2 More than Methods for producing cell products.

21. The method for producing a cell product according to claim 20, wherein the porous membrane is a hollow fiber membrane.

22. The method for producing a cell product according to claim 21 , wherein the hollow fiber membrane has a substantially uniform structure in the membrane thickness direction from the primary side to the secondary side.

23. The method for producing a cell product according to claim 21, wherein the pore size of the pores in the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

24. The method for producing a cell product according to claim 21 , wherein the hollow fiber membrane is made of a synthetic polymer membrane.

25. The method for producing a cell product according to claim 24, wherein the synthetic polymer is polyvinylidene fluoride.

26. The shear stress is measured based on the viscosity of the culture medium, and the measured shear stress is 4.0 N / m 2 The method for producing a cell product described in claim 20, further comprising controlling a flow rate of the culture solution filtered through the porous membrane in a direction parallel to the membrane surface so as to achieve the above.

27. The method for producing a cell product according to claim 20, wherein the culture medium that is not filtered through the porous membrane is returned to the cell culture vessel.

28. 21. The method of claim 20, wherein the product is an antibody.

29. 21. The method of claim 20, wherein the cells are in perfusion culture.

30. filtering a culture medium of the cells through a porous membrane to obtain a product of the cells; The porous membrane has a liquid-contacting surface having at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less; and The liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis ratio of 1.8 or less; and The shear stress due to the flow of the culture medium on the liquid-contacting surface is 4.0 N / m 2 A method for suppressing a decrease in membrane permeability of a cell product by:

31. The method for suppressing a decrease in membrane permeability of a cellular product described in claim 30, wherein the porous membrane has at least one selected from the group consisting of an average pore size of 1 μm or more at the liquid-contacting surface, and maximum / minimum values ​​of the average pore size in three or more membrane thickness directions.

32. The method for suppressing a decrease in membrane permeability of a cell product described in claim 30, wherein the porous membrane has at least one selected from the group consisting of an average pore size of 10 μm or less at the liquid contact surface, and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10.

33. The method for suppressing a decrease in membrane permeability of a cell product described in claim 31, wherein the porous membrane is a hollow fiber membrane.

34. The method for suppressing a decrease in membrane permeability of a cell product according to claim 33, wherein the hollow fiber membrane has a gradient structure in which the average pore size decreases in the membrane thickness direction from the primary side to the secondary side.

35. The method for suppressing a decrease in membrane permeability of a cell product according to claim 33, wherein the blocking pore size of the pores in the hollow fiber membrane is 0.05 μm or more and 20 μm or less.

36. The method for suppressing a decrease in membrane permeability of a cell product according to claim 33, wherein the hollow fiber membrane is made of a synthetic polymer membrane.

37. The method for suppressing a decrease in membrane permeability of a cell product described in claim 36, wherein the synthetic polymer is polysulfone.

38. The method for suppressing a decrease in membrane permeability of a cellular product according to claim 33, wherein the hollow fiber membrane has a coarse layer and a dense layer.

39. The method for suppressing a decrease in membrane permeability of a cell product described in claim 32, wherein the porous membrane is a hollow fiber membrane.

40. The method for suppressing a decrease in membrane permeability of a cell product as described in claim 39, wherein the hollow fiber membrane has a substantially uniform homogeneous structure in the membrane thickness direction from the primary side to the secondary side.

41. The method for suppressing a decrease in membrane permeability of a cell product according to claim 39, wherein the blocking pore size of the pores in the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

42. The method for suppressing a decrease in membrane permeability of a cell product described in claim 39, wherein the hollow fiber membrane is made of a synthetic polymer membrane.

43. The method for suppressing a decrease in membrane permeability of a cellular product described in claim 42, wherein the synthetic polymer is polyvinylidene fluoride.

44. The shear stress is measured based on the viscosity of the culture medium, and the measured shear stress is 4.0 N / m 2 The method for suppressing a decrease in membrane permeability of a cellular product described in claim 30, further comprising controlling a flow rate of the culture solution filtered through the porous membrane in a direction parallel to the membrane surface so as to be as follows.

45. The method for suppressing a decrease in membrane permeability of a cell product according to claim 30, wherein the culture medium that has not been filtered through the porous membrane is returned to the cell culture vessel.

46. The method for inhibiting a decrease in membrane permeability of a cellular product according to claim 30, wherein the product is an antibody.

47. The method for suppressing a decrease in membrane permeability of a cellular product described in claim 30, wherein the cells are in perfusion culture.

48. The density of the cells contained in the culture medium is 8×10 7 The method for suppressing a decrease in membrane permeability of a cellular product described in claim 32, wherein the decrease is at least 100 μg / mL.

49. filtering a culture medium of the cells through a porous membrane to obtain a product of the cells; The porous membrane has a liquid-contacting surface having at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less; and The liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 or less and a pore major axis / minor axis ratio of 1.8 or more; and The shear stress due to the flow of the culture medium on the liquid-contacting surface is 4.0 N / m 2 By carrying out the above steps, a decrease in membrane permeability of cell products can be suppressed.

50. The method for suppressing a decrease in membrane permeability of a cellular product described in claim 49, wherein the porous membrane is a hollow fiber membrane.

51. The method for suppressing a decrease in membrane permeability of a cell product as described in claim 50, wherein the hollow fiber membrane has a substantially uniform homogeneous structure in the membrane thickness direction from the primary side to the secondary side.

52. The method for suppressing a decrease in membrane permeability of a cell product described in claim 50, wherein the blocking pore size of the pores of the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

53. The method for suppressing a decrease in membrane permeability of a cell product described in claim 50, wherein the hollow fiber membrane is made of a synthetic polymer membrane.

54. The method for suppressing a decrease in membrane permeability of a cellular product described in claim 53, wherein the synthetic polymer is polyvinylidene fluoride.

55. The shear stress is measured based on the viscosity of the culture medium, and the measured shear stress is 4.0 N / m 2 The method for suppressing a decrease in membrane permeability of a cellular product described in claim 49, further comprising controlling the flow rate of the culture solution filtered through the porous membrane in a direction parallel to the membrane surface so as to be equal to or greater than the above.

56. The method for suppressing a decrease in membrane permeability of a cell product described in claim 49, wherein the culture medium that has not been filtered through the porous membrane is returned to the cell culture vessel.

57. The method for inhibiting a decrease in membrane permeability of a cellular product described in claim 49, wherein the product is an antibody.

58. The method for inhibiting a decrease in membrane permeability of a cellular product described in claim 49, wherein the cells are in perfusion culture.

59. A culture vessel for culturing cells; a porous membrane for filtering the culture medium of the cells to obtain a product of the cells; A pump for sending the culture medium from the culture tank to the porous membrane; The shear stress due to the flow of the culture solution on the liquid-contacting surface of the porous membrane is 4.0 N / m 2 A control unit that controls the pump so as to: Equipped with The liquid-contacting surface has at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, The liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis ratio of 1.8 or less. Cellular product manufacturing systems.

60. The cell product manufacturing system of claim 59, wherein the porous membrane has at least one selected from the group consisting of an average pore size of 1 μm or more at the liquid-contacting surface and maximum / minimum average pore size in three or more membrane thickness directions.

61. The cell product manufacturing system of claim 59, wherein the porous membrane has at least one selected from the group consisting of an average pore size of 10 μm or less at the liquid contact surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 to 10.

62. The cellular product manufacturing system of claim 60, wherein the porous membrane is a hollow fiber membrane.

63. The cell product manufacturing system of claim 62, wherein the hollow fiber membrane has a gradient structure in which the average pore size decreases in the membrane thickness direction from the primary side to the secondary side.

64. The cell product manufacturing system of claim 62, wherein the pore size of the pores in the hollow fiber membrane is 0.05 μm or more and 20 μm or less.

65. The cell product manufacturing system of claim 62, wherein the hollow fiber membrane is made of a synthetic polymer membrane.

66. The cellular product production system of claim 65 , wherein the synthetic polymer is polysulfone.

67. 63. The cellular product manufacturing system of claim 62, wherein the hollow fiber membrane has a coarse layer and a dense layer.

68. The cellular product manufacturing system of claim 61 , wherein the porous membrane is a hollow fiber membrane.

69. The cell product manufacturing system of claim 68, wherein the hollow fiber membrane has a substantially uniform homogeneous structure in the membrane thickness direction from the primary side to the secondary side.

70. The cell product manufacturing system of claim 68, wherein the pore size of the pores in the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

71. The cell product manufacturing system of claim 68, wherein the hollow fiber membrane is made of a synthetic polymer membrane.

72. The cellular product manufacturing system of claim 71 , wherein the synthetic polymer is polyvinylidene fluoride.

73. The control unit measures the shear stress based on the viscosity of the culture solution, and the measured shear stress is 4.0 N / m 2 The cell product manufacturing system of claim 59, wherein the flow rate of the culture solution filtered through the porous membrane in a direction parallel to the membrane surface is controlled so as to be as follows:

74. The cell product manufacturing system of claim 59 , wherein the control unit accepts input of data on the viscosity of the culture medium.

75. The cell product manufacturing system of claim 59, further comprising a flow path for returning the culture solution that was not filtered through the porous membrane to the culture tank.

76. 60. The cellular product production system of claim 59, wherein the product is an antibody.

77. 60. The cellular product manufacturing system of claim 59, wherein the cells are in perfusion culture.

78. The density of the cells contained in the culture medium is 8×10 7 62. The system for producing a cell product according to claim 61, wherein the cell product is 0.1 to 1.0 cells / mL or more.

79. A culture vessel for culturing cells; a porous membrane for filtering the culture medium of the cells to obtain a product of the cells; A pump for sending the culture medium from the culture tank to the porous membrane; The shear stress due to the flow of the culture solution on the liquid-contacting surface of the porous membrane is 4.0 N / m 2 A control unit that controls the pump so as to achieve the above; Equipped with The liquid-contacting surface has at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, The liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 or less and a pore major axis / minor axis ratio of 1.8 or more. Cellular product manufacturing systems.

80. 80. The cellular product manufacturing system of claim 79, wherein the porous membrane is a hollow fiber membrane.

81. The cell product manufacturing system of claim 80, wherein the hollow fiber membrane has a substantially uniform homogeneous structure in the membrane thickness direction from the primary side to the secondary side.

82. The cell product manufacturing system of claim 80, wherein the pore size of the pores in the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

83. The cell product manufacturing system of claim 80, wherein the hollow fiber membrane is made of a synthetic polymer membrane.

84. The cellular product manufacturing system of claim 83, wherein the synthetic polymer is polyvinylidene fluoride.

85. The control unit measures the shear stress based on the viscosity of the culture solution, and the measured shear stress is 4.0 N / m 2 The cell product manufacturing system of claim 79, wherein the flow rate of the culture solution filtered through the porous membrane in a direction parallel to the membrane surface is controlled so as to be as described above.

86. The cell product manufacturing system of claim 79, wherein the control unit accepts input of data on the viscosity of the culture medium.

87. The cell product manufacturing system of claim 79, further comprising a flow path for returning the culture solution that was not filtered through the porous membrane to the culture tank.

88. 80. The cellular product production system of claim 79, wherein the product is an antibody.

89. 80. The cellular product manufacturing system of claim 79, wherein the cells are in perfusion culture.

90. filtering a culture medium of the cells through a porous membrane to obtain a product of the cells; The porous membrane has a liquid-contacting surface having at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less; and The liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis ratio of 1.8 or less; and The porous membrane has at least one selected from the group consisting of an average pore size of 10 μm or less on the liquid-contacting surface and a maximum / minimum value of the average pore size in the thickness direction of the membrane of 1 to 10; and The density of cells contained in the culture medium to be filtered is 8 x 10 7 cells / mL or more; Methods for producing cell products.

91. The method for producing a cell product according to claim 90, wherein the porous membrane is a hollow fiber membrane.

92. The method for producing a cell product of claim 90, wherein the culture medium that is not filtered through the porous membrane is returned to the cell culture vessel.

93. 91. The method of claim 90, wherein the product is an antibody.

94. 91. The method of claim 90, wherein the cells are in perfusion culture.

95. filtering a culture medium of the cells through a porous membrane to obtain a product of the cells; The porous membrane has a liquid-contacting surface having at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less; and The liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis ratio of 1.8 or less; and The porous membrane has at least one selected from the group consisting of an average pore size of 10 μm or less on the liquid-contacting surface and a maximum / minimum value of the average pore size in the thickness direction of the membrane of 1 to 10; and The density of cells contained in the culture medium to be filtered is 8 x 10 7 cells / mL or more, thereby suppressing a decrease in membrane permeability of cell products.

96. The method for suppressing a decrease in membrane permeability of a cellular product described in claim 95, wherein the porous membrane is a hollow fiber membrane.

97. The method for suppressing a decrease in membrane permeability of a cell product described in claim 95, wherein the culture medium that has not been filtered through the porous membrane is returned to the cell culture vessel.

98. A method for inhibiting a decrease in membrane permeability of a cellular product as described in claim 95, wherein the product is an antibody.

99. The method for inhibiting a decrease in membrane permeability of a cellular product described in claim 95, wherein the cells are in perfusion culture.

100. A culture vessel for culturing cells; a porous membrane for filtering the culture medium of the cells to obtain a product of the cells; A pump for sending the culture medium from the culture tank to the porous membrane; Equipped with The liquid-contacting surface of the porous membrane has at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size / fiber size ratio of 1.3 or less, The liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03 and a pore major axis / minor axis ratio of 1.8 or less; and The porous membrane has at least one selected from the group consisting of an average pore size of 10 μm or less on the liquid-contacting surface and a maximum / minimum value of the average pore size in the thickness direction of the membrane of 1 to 10; and The density of cells contained in the culture medium to be filtered is 8 x 10 7 cells / mL or more; Cellular product manufacturing systems.

101. The cellular product manufacturing system of claim 100, wherein the porous membrane is a hollow fiber membrane.

102. The cell product manufacturing system of claim 100, wherein the culture medium that is not filtered through the porous membrane is returned to the cell culture vessel.

103. 101. The system for producing a cellular product of claim 100, wherein the product is an antibody.

104. 101. The cellular product manufacturing system of claim 100, wherein the cells are in perfusion culture.