Method for producing cell product, method for purifying cell product, method for suppressing reduction in membrane transmittance of cell product, system for producing cell product, and system for purifying cell product

Abstract

A method for producing a cell product, which comprises a step for filtering a cell culture solution with a porous membrane to obtain a cell product, the porous membrane having a liquid-contacting surface having at least one selected from the group consisting of an aperture ratio of 57.5% or less, a pore diameter having a coefficient of variation 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 degree of structural anisotropy of 0.97-1.03 and a major diameter / minor diameter of pores of 1.8 or less, and the shear stress generated by the flow of the culture solution at the liquid contact surface is 4.0 N / m2 or less.

Description

Technical Field

[0001] The present invention relates to filtration technology, and relates to a method for manufacturing 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 cell product manufacturing system, and a cell product purification system. Background Art

[0002] Cell culture technology is an essential technology for manufacturing various biopharmaceuticals such as antibodies, growth hormones, and insulin, and has made a great contribution to recent medical progress. Among biopharmaceuticals, antibody drugs have attracted particular attention. Efficiently and stably producing monoclonal antibodies by culturing antibody-producing cells is an important industrial issue.

[0003] Industrial cell culture methods for producing useful cell products such as antibodies are roughly divided into two types: adherent culture method and suspension culture (floating culture) method. In the adherent culture method, cells adhere to the inner surface of the culture tank. In the suspension culture method, cells float in the culture solution. Among these, the suspension culture method has become the mainstream because of its ease of large-scale production and ease of control at a large scale.

[0004] In the method of culturing cells by suspension culture, for example, a method has been proposed in which a stirring mechanism is provided in a culture tank such as a rotating bottle to make the cells float, and a magnetic stirrer or a mechanically driven shaft-shaped impeller is used as the stirring mechanism. However, in existing suspension culture methods, cells are sometimes cultured without supplementing nutrient components, and growth inhibitory substances such as lactic acid accumulate. Therefore, there are cases where cells stop growing in a state of low cell density.

[0005] On the other hand, in the suspension culture method, in order to culture cells in large quantities and at a high density and continuously produce cell products efficiently, a method has been proposed in which fresh culture solution is supplied to the culture tank at a certain speed while the old culture solution containing the cell product is filtered and discharged from the culture tank at a certain speed to culture the cells. This type of culture is generally referred to as continuous culture or perfusion culture (for example, refer to Patent Documents 1 to 5). During continuous culture, control can be performed in such a way that the amount of culture solution supplied to the culture tank is the same as the amount of culture solution discharged from the culture tank. In continuous culture, it is important to effectively separate the cells in the culture solution from the old culture solution and the cell product for a long time, take out the old culture solution and the cell product outside the culture tank, and continuously maintain the cell growth environment in the culture tank under the optimal conditions for a long time.

[0006] Prior Art Documents

[0007] Patent Documents

[0008] Patent Document 1: Japanese Unexamined Patent Application Publication No. 2018-76291

[0009] Patent Document 2: Japanese Unexamined Patent Application Publication No. 2009-45019

[0010] Patent Document 3: Japanese Unexamined Patent Application Publication No. 2021-48776

[0011] Patent Document 4: Japanese Patent No. 5696479

[0012] Patent Document 5: Japanese Patent Application Laid-Open No. 2022-516516 Summary of the Invention

[0013] Problems to be Solved by the Invention

[0014] In continuous cultivation, a porous membrane is used to separate cells in the culture solution of a culture tank from the old culture solution and cell products. However, there are the following problems: as the time of filtration using the porous membrane accumulates, substances accumulate and adhere to the surface and pores of the porous membrane or fouling occurs, and the cell product permeation rate of the porous membrane decreases. Therefore, the subject of the present invention is to provide a method for manufacturing a cell product, a method for purifying a cell product, a method for suppressing a decrease in the membrane permeation rate of a cell product, a manufacturing system for a cell product, and a purification system for a cell product that can suppress a decrease in the cell product permeation rate of a porous membrane.

[0015] Solutions to the Problems

[0016] [1] A method for manufacturing a cell product, which includes a step of obtaining a product of cells by filtering a culture solution of cells with a porous membrane, the porous membrane having a liquid contact surface, the liquid contact surface having at least any one selected from the group consisting of an opening ratio 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 the liquid contact surface having at least any one selected from the group consisting of a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and setting the shear stress generated by the flow of the culture solution at the liquid contact surface to 4.0 N / m 2 or less.

[0017] In this method for manufacturing a cell product, the liquid contact surface may have an opening ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0018] In this method for manufacturing a cell product, the liquid contact surface may have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0019] In the method for manufacturing the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0020] In the method for manufacturing the cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0021] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0022] In the method for manufacturing the cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0023] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0024] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a major axis / minor axis of the pore of 1.8 or less.

[0025] In the method for manufacturing the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a major axis / minor axis of the pore of 1.8 or less.

[0026] In the method for manufacturing the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of the pore of 1.8 or less.

[0027] In the method for manufacturing the cell product, the liquid contact surface may also 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 contact surface may have a major axis / minor axis of the pore of 1.8 or less.

[0028] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of the pore of 1.8 or less.

[0029] In the method for manufacturing the cell product, the liquid contact surface may also 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 contact surface has a major axis / minor axis of the pore of 1.8 or less.

[0030] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface has a major axis / minor axis of the pore of 1.8 or less.

[0031] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less.

[0032] In the method for manufacturing the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less.

[0033] In the method for manufacturing the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less.

[0034] In the method for manufacturing the cell product, the liquid contact surface may also 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 contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less.

[0035] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less.

[0036] In the method for manufacturing the cell product, the liquid contact surface may also 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 contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less.

[0037] In the method for manufacturing the cell product, the liquid contact surface may have an opening ratio 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 the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less.

[0038] [2] The method for manufacturing the cell product according to [1], wherein the porous membrane has at least any one selected from the group consisting of an average pore diameter of 1 μm or more on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 3 or more.

[0039] In the method for manufacturing the cell product, the porous membrane may have an average pore diameter of 1 μm or more on the liquid contact surface.

[0040] In the method for manufacturing the cell product, the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 3 or more.

[0041] In the method for manufacturing the cell product, the porous membrane may have an average pore diameter of 1 μm or more on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 3 or more.

[0042] [3] The method for manufacturing the cell product according to [1], wherein the porous membrane has at least any one selected from the group consisting of an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0043] In the method for manufacturing the cell product, the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0044] In the method for manufacturing the cell product, the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0045] In the method for manufacturing the cell product, the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0046] [4] The method for manufacturing the cell product according to [2], wherein the porous membrane is a hollow fiber membrane.

[0047] [5] The method for manufacturing the cell product according to [4], wherein the hollow fiber membrane has an inclined structure in which the average pore diameter decreases from the primary side to the secondary side in the membrane thickness direction.

[0048] [6] The method for producing a cell product according to [4] or [5], wherein the exclusion pore diameter of the pores of the hollow fiber membrane is 0.05 μm or more and 20 μm or less.

[0049] [7] The method for producing a cell product according to any one of [4] to [6], wherein the hollow fiber membrane comprises a synthetic polymer membrane.

[0050] [8] The method for producing a cell product according to [7], wherein the synthetic polymer is polysulfone.

[0051] [9] The 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.

[0052]

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

[0053]

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

[0054]

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

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

[0055]

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

[11] or

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

[0056]

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

[11] to

[13] , wherein the hollow fiber membrane comprises a synthetic polymer membrane.

[0057]

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

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

[0058]

[16] The method for producing a cell product according to [3] or any one of

[11] to

[15] , wherein the density of the cells contained in the culture solution to be filtered is 8×10 7 cells / mL or more.

[0059]

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

[16] , further comprising the following step: measuring the shear stress based on the viscosity of the culture solution, and controlling the flow velocity in the direction parallel to the membrane surface of the culture solution filtered through the porous membrane so that the measured shear stress becomes 4.0 N / m 2 or less.

[0060]

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

[17] , wherein the culture solution not filtered through the hollow fiber membrane is returned to the cell culture tank.

[0061]

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

[18] , wherein the product is an antibody.

[0062]

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

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

[0063]

[21] A method for purifying a cell product, which comprises a step of purifying the cell product by filtering the culture solution of the cells through a porous membrane, the porous membrane having a liquid contact surface, the liquid contact surface having at least any one selected from the group consisting of an opening ratio 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 the liquid contact surface having at least any one selected from the group consisting of a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and setting the shear stress generated by the flow of the culture solution at the liquid contact surface to 4.0 N / m 2 or less.

[0064] In the method for purifying the cell product, the liquid contact surface may have an opening ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0065] In the method for purifying the cell product, the liquid contact surface may have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0066] In the method for purifying the cell product, the liquid contact surface may have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0067] In the method for purifying the cell product, the liquid contact 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0068] In the method for purifying the cell product, the liquid contact surface may have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0069] In the method for purifying the cell product, the liquid contact surface may also 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 contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0070] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0071] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less.

[0072] In the method for purifying the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less.

[0073] In the method for purifying the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less.

[0074] In the method for purifying the cell product, the liquid contact surface may also 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 contact surface has a major axis / minor axis of the pores of 1.8 or less.

[0075] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less.

[0076] In the method for purifying the cell product, the liquid contact surface may also 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 contact surface has a major axis / minor axis of the pores of 1.8 or less.

[0077] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less.

[0078] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less.

[0079] In the method for purifying the cell product, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less.

[0080] In the method for purifying the cell product, the liquid contact surface may also have a pore size / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less.

[0081] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less.

[0082] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less.

[0083] In the method for purifying the cell product, the liquid contact surface may also 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, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less.

[0084] In the method for purifying the cell product, the liquid contact surface may also 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 of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less.

[0085]

[22] In the method for purifying the cell product according to

[21] , the porous membrane has at least any one selected from the group consisting of a maximum value / minimum value of an average pore size of 1 μm or more on the liquid contact surface and an average pore size in the membrane thickness direction of 3 or more.

[0086] In the method for purifying the cell product, the porous membrane may have an average pore size of 1 μm or more on the liquid contact surface.

[0087] In the method for purifying the cell product, the porous membrane may have a maximum value / minimum value of an average pore size in the membrane thickness direction of 3 or more.

[0088] In the method for purifying the cell product, the porous membrane may have an average pore diameter of more than 1 μm on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 3 or more.

[0089]

[23] In the method for purifying the cell product according to

[21] , wherein the porous membrane has at least any one selected from the group consisting of an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0090] In the method for purifying the cell product, the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0091] In the method for purifying the cell product, the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0092] In the method for purifying the cell product, the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0093]

[24] In the method for purifying the cell product according to

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

[0094]

[25] In the method for purifying the cell product according to

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

[0095]

[26] In the method for purifying the cell product according to

[24] or

[25] , wherein the exclusion pore diameter of the pores of the hollow fiber membrane is 0.05 μm or more and 20 μm or less.

[0096]

[27] In the method for purifying the cell product according to any one of

[24] to

[26] , wherein the hollow fiber membrane comprises a synthetic polymer membrane.

[0097]

[28] In the method for purifying the cell product according to

[27] , wherein the synthetic polymer is polysulfone.

[0098]

[29] In the method for purifying the cell product according to any one of

[24] to

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

[0099]

[30] In the method for purifying the cell product according to

[22] or any one of

[24] to

[29] , wherein the density of the cells contained in the culture solution to be filtered is 5×10 7 cells / mL or less.

[0100]

[31] The purification method of the cell product according to

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

[0101]

[32] The purification method of the cell product according to

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

[0102]

[33] The purification method of the cell product according to

[31] or

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

[0103]

[34] The purification method of the cell product according to any one of

[31] to

[33] , wherein the hollow fiber membrane comprises a synthetic polymer membrane.

[0104]

[35] The purification method of the cell product according to

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

[0105]

[36] The purification method of the cell product according to

[23] or any one of

[31] to

[35] , wherein the density of the cells contained in the culture solution to be filtered is 8×10 7 cells / mL or more.

[0106]

[37] The purification method of the cell product according to any one of

[21] to

[36] , further comprising the following step: measuring the shear stress based on the viscosity of the culture solution, and controlling the flow rate in the direction parallel to the membrane surface of the culture solution filtered through the porous membrane so that the measured shear stress becomes 4.0 N / m 2 or less.

[0107]

[38] The purification method of the cell product according to any one of

[21] to

[37] , wherein the culture solution not filtered through the hollow fiber membrane is returned to the cell culture tank.

[0108]

[39] The purification method of the cell product according to any one of

[21] to

[38] , wherein the product is an antibody.

[0109]

[40] The purification method of the cell product according to any one of

[21] to

[39] , wherein the cells are subjected to perfusion culture.

[0110]

[41] A method for manufacturing a cell product, which includes the step of filtering a culture solution of cells with a porous membrane to obtain the cell product. The porous membrane has a liquid contact surface, and the liquid contact surface has at least any one selected from the group consisting of an aperture ratio 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 the liquid contact surface has at least any one selected from the group consisting of a structural anisotropy degree of 0.97 or less and a major axis / minor axis of pores of 1.8 or more. And the shear stress generated by the flow of the culture solution at the liquid contact surface is set to 4.0 N / m 2 or more.

[0111] In this method for manufacturing a cell product, it is also possible that the liquid contact surface has an aperture ratio of 57.5% or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or less.

[0112] In this method for manufacturing a cell product, it is also possible that the liquid contact surface has a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or less.

[0113] In this method for manufacturing a cell product, it is also possible that the liquid contact surface has a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or less.

[0114] In this method for manufacturing a cell product, it is also possible that the liquid contact surface has an aperture ratio of 57.5% or less and a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or less.

[0115] In this method for manufacturing a cell product, it is also possible that the liquid contact surface has an aperture ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or less.

[0116] In this method for manufacturing a cell product, it is also possible that the liquid contact surface has 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 contact surface has a structural anisotropy degree of 0.97 or less.

[0117] In this method for manufacturing a cell product, it is also possible that the liquid contact surface has an aperture ratio 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 the liquid contact surface has a structural anisotropy degree of 0.97 or less.

[0118] In this method for manufacturing a cell product, it is also possible that the liquid contact surface has an aperture ratio of 57.5% or less, and the liquid contact surface has a major axis / minor axis of pores of 1.8 or more.

[0119] In the method for manufacturing the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or more.

[0120] In the method for manufacturing the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or more.

[0121] In the method for manufacturing the cell product, the liquid contact surface may also 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 contact surface may have a major axis / minor axis of the pores of 1.8 or more.

[0122] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or more.

[0123] In the method for manufacturing the cell product, the liquid contact surface may also 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 contact surface may have a major axis / minor axis of the pores of 1.8 or more.

[0124] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or more.

[0125] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0126] In the method for manufacturing the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0127] In the method for manufacturing the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0128] In the method for producing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, and a structure anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0129] In the method for producing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and a structure anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0130] In the method for producing the cell product, the liquid contact surface may also 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 structure anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0131] In the method for producing the cell product, the liquid contact surface may also have an opening ratio 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 structure anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0132]

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

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

[0133]

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

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

[0134]

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

[42] or

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

[0135]

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

[42] to

[44] , wherein the hollow fiber membrane comprises a synthetic polymer membrane.

[0136]

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

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

[0137]

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

[41] to

[46] , further comprising the following step: measuring the shear stress based on the viscosity of the culture solution, and controlling the flow velocity in the direction parallel to the membrane surface of the culture solution filtered through the porous membrane so that the measured shear stress becomes 4.0 N / m 2 or more.

[0138]

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

[41] to

[47] , wherein the culture solution not filtered by the hollow fiber membrane is returned to the cell culture tank.

[0139]

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

[41] to

[48] , wherein the product is an antibody.

[0140]

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

[41] to

[49] , wherein the cells are subjected to perfusion culture.

[0141]

[51] A method for purifying a cell product, which comprises a step of purifying the cell product by filtering the culture solution of the cells with a porous membrane, the porous membrane having a liquid contact surface, the liquid contact surface having at least any one selected from the group consisting of an opening ratio 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 the liquid contact surface having at least any one selected from the group consisting of a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pore of 1.8 or more, and setting the shear stress generated by the flow of the culture solution at the liquid contact surface to 4.0 N / m 2 or more.

[0142] In the method for purifying the cell product, the liquid contact surface may have an opening ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or less.

[0143] In the method for purifying the cell product, the liquid contact surface may have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or less.

[0144] In the method for purifying the cell product, the liquid contact surface may have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or less.

[0145] In the method for purifying the cell product, the liquid contact 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 contact surface may have a structural anisotropy degree of 0.97 or less.

[0146] In the method for purifying the cell product, the liquid contact surface may have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or less.

[0147] In the method for purifying the cell product, the liquid contact surface may also 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, and the liquid contact surface has a structural anisotropy degree of 0.97 or less.

[0148] In the method for purifying the cell product, the liquid contact surface may also 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 of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or less.

[0149] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a major axis / minor axis of pores of 1.8 or more.

[0150] In the method for purifying the cell product, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a major axis / minor axis of pores of 1.8 or more.

[0151] In the method for purifying the cell product, the liquid contact surface may also have a pore size / fiber diameter of 1.3 or less, and the liquid contact surface has a major axis / minor axis of pores of 1.8 or more.

[0152] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a major axis / minor axis of pores of 1.8 or more.

[0153] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size / fiber diameter of 1.3 or less, and the liquid contact surface has a major axis / minor axis of pores of 1.8 or more.

[0154] In the method for purifying the cell product, the liquid contact surface may also 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, and the liquid contact surface has a major axis / minor axis of pores of 1.8 or more.

[0155] In the method for purifying the cell product, the liquid contact surface may also 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 of 1.3 or less, and the liquid contact surface has a major axis / minor axis of pores of 1.8 or more.

[0156] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or less and a major axis / minor axis of pores of 1.8 or more.

[0157] In the method for purifying the cell product, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0158] In the method for purifying the cell product, the liquid contact surface may also have a pore size / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0159] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0160] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0161] In the method for purifying the cell product, the liquid contact surface may also 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, and the liquid contact surface may have a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0162] In the method for purifying the cell product, the liquid contact surface may also 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 of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0163]

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

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

[0164]

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

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

[0165]

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

[52] or

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

[0166]

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

[52] to

[54] , wherein the hollow fiber membrane comprises a synthetic polymer membrane.

[0167]

[56] The purification method of the cell product according to

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

[0168]

[57] The purification method of the cell product according to any one of

[51] to

[56] , further comprising the following step: measuring the shear stress based on the viscosity of the culture solution, and controlling the flow velocity of the culture solution filtered through the porous membrane in the direction parallel to the membrane surface in such a manner that the measured shear stress becomes 4.0 N / m 2 or more.

[0169]

[58] The purification method of the cell product according to any one of

[51] to

[57] , wherein the culture solution not filtered through the hollow fiber membrane is returned to the cell culture tank.

[0170]

[59] The purification method of the cell product according to any one of

[51] to

[58] , wherein the product is an antibody.

[0171]

[60] The purification method of the cell product according to any one of

[51] to

[59] , wherein the cells are subjected to perfusion culture.

[0172]

[61] A method for inhibiting the reduction of the membrane permeability of a cell product, comprising the step of filtering the culture solution of the cells through a porous membrane to obtain the cell product, wherein the porous membrane has a liquid contact surface, and the liquid contact surface has at least any one selected from the group consisting of an opening ratio 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 the liquid contact surface has at least any one selected from the group consisting of a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the shear stress generated by the flow of the culture solution at the liquid contact surface is set to 4.0 N / m 2 or less, thereby inhibiting the reduction of the membrane permeability of the cell product.

[0173] In this method for inhibiting the reduction of the membrane permeability of the cell product, the liquid contact surface may have an opening ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0174] In this method for inhibiting the reduction of the membrane permeability of the cell product, the liquid contact surface may have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0175] In this method for inhibiting the reduction of the membrane permeability of the cell product, the liquid contact surface may have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0176] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, and a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0177] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0178] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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 degree of 0.97 or more and 1.03 or less.

[0179] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio 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 structural anisotropy degree of 0.97 or more and 1.03 or less.

[0180] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less, and a major axis / minor axis of the pores of 1.8 or less.

[0181] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and a major axis / minor axis of the pores of 1.8 or less.

[0182] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and a major axis / minor axis of the pores of 1.8 or less.

[0183] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter with a coefficient of variation of 0.5 or less, and a major axis / minor axis of the pores of 1.8 or less.

[0184] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and a major axis / minor axis of the pores of 1.8 or less.

[0185] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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 contact surface may have a major axis / minor axis of pores of 1.8 or less.

[0186] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio 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 the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less.

[0187] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less.

[0188] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less.

[0189] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less.

[0190] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less.

[0191] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less.

[0192] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less.

[0193] In the method for reducing the membrane permeability of cell products, the liquid contact 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 of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less.

[0194]

[62] The method for reducing the membrane permeability of cell products according to

[61] , wherein the porous membrane has at least any one selected from the group consisting of an average pore size of 1 μm or more on the liquid contact surface and a maximum value / minimum value of the average pore size in the membrane thickness direction of 3 or more.

[0195] In the method for reducing the membrane permeability of cell products, the porous membrane may have an average pore size of 1 μm or more on the liquid contact surface.

[0196] In the method for reducing the membrane permeability of cell products, the porous membrane may have a maximum value / minimum value of the average pore size in the membrane thickness direction of 3 or more.

[0197] In the method for reducing the membrane permeability of cell products, the porous membrane may have an average pore size of 1 μm or more on the liquid contact surface and a maximum value / minimum value of the average pore size in the membrane thickness direction of 3 or more.

[0198]

[63] The method for reducing the membrane permeability of cell products according to

[61] , wherein the porous membrane has at least any one selected from the group consisting of an average pore size of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0199] In the method for reducing the membrane permeability of cell products, the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0200] In the method for reducing the membrane permeability of cell products, the porous membrane may have a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0201] In the method for reducing the membrane permeability of cell products, the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0202]

[64] The method for reducing the membrane permeability of cell products according to

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

[0203]

[65] The method for suppressing the reduction in the membrane permeability of cell products according to

[64] , wherein the hollow fiber membrane has an inclined structure with a gradually decreasing average pore size from the primary side to the secondary side in the membrane thickness direction.

[0204]

[66] The method for suppressing the reduction in the membrane permeability of cell products according to

[64] or

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

[0205]

[67] The method for suppressing the reduction in the membrane permeability of cell products according to any one of

[64] to

[66] , wherein the hollow fiber membrane comprises a synthetic polymer membrane.

[0206]

[68] The method for suppressing the reduction in the membrane permeability of cell products according to

[67] , wherein the synthetic polymer is polysulfone.

[0207]

[69] The method for suppressing the reduction in the membrane permeability of cell products according to any one of

[64] to

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

[0208]

[70] The method for suppressing the reduction in the membrane permeability of cell products according to

[62] or any one of

[64] to

[69] , wherein the density of the cells contained in the culture solution to be filtered is 5×10 7 cells / mL or less.

[0209]

[71] The method for suppressing the reduction in the membrane permeability of cell products according to

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

[0210]

[72] The method for suppressing the reduction in the membrane permeability of cell products according to

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

[0211]

[73] The method for suppressing the reduction in the membrane permeability of cell products according to

[71] or

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

[0212]

[74] The method for suppressing the reduction in the membrane permeability of cell products according to any one of

[71] to

[73] , wherein the hollow fiber membrane comprises a synthetic polymer membrane.

[0213]

[75] The method for suppressing the reduction in the membrane permeability of cell products according to

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

[0214]

[76] The method for suppressing the reduction in the membrane permeability of a cell product according to any one of

[63] or

[71] to

[75] , wherein the density of the cells contained in the culture solution to be filtered is 8×10 7 cells / mL or more.

[0215]

[77] The method for suppressing the reduction in the membrane permeability of a cell product according to any one of

[61] to

[76] , further comprising the step of: measuring the shear stress based on the viscosity of the culture solution, and controlling the flow velocity in the direction parallel to the membrane surface of the culture solution filtered through the porous membrane so that the measured shear stress becomes 4.0 N / m 2 or less.

[0216]

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

[61] to

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

[0217]

[79] The method for suppressing the reduction in the membrane permeability of a cell product according to any one of

[61] to

[78] , wherein the product is an antibody.

[0218]

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

[61] to

[79] , wherein the cells are subjected to perfusion culture.

[0219]

[81] A method for suppressing the reduction in the membrane permeability of a cell product, which includes the step of filtering the culture solution of cells through a porous membrane to obtain the product of the cells. The porous membrane has a liquid contact surface, and the liquid contact surface has at least any one selected from the group consisting of an aperture ratio 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 the liquid contact surface has at least any one selected from the group consisting of a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pore of 1.8 or more. And the shear stress generated by the flow of the culture solution at the liquid contact surface is set to 4.0 N / m 2 or more, thereby suppressing the reduction in the membrane permeability of the cell product.

[0220] In this method for suppressing the reduction in the membrane permeability of a cell product, the liquid contact surface may have an aperture ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or less.

[0221] In this method for suppressing the reduction in the membrane permeability of a cell product, the liquid contact surface may have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or less.

[0222] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less and a structural anisotropy degree of 0.97 or less.

[0223] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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 contact surface has a structural anisotropy degree of 0.97 or less.

[0224] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or less.

[0225] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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 contact surface has a structural anisotropy degree of 0.97 or less.

[0226] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio 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 the liquid contact surface has a structural anisotropy degree of 0.97 or less.

[0227] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a major axis / minor axis of pores of 1.8 or more.

[0228] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface has a major axis / minor axis of pores of 1.8 or more.

[0229] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a major axis / minor axis of pores of 1.8 or more.

[0230] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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 contact surface has a major axis / minor axis of pores of 1.8 or more.

[0231] In the method for reducing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less, a pore diameter / fiber diameter of 1.3 or less, and a major axis / minor axis of the pores of 1.8 or more.

[0232] In the method for reducing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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 major axis / minor axis of the pores of 1.8 or more.

[0233] In the method for reducing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio 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 major axis / minor axis of the pores of 1.8 or more.

[0234] In the method for reducing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less, and a degree of structural anisotropy of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0235] In the method for reducing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and a degree of structural anisotropy of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0236] In the method for reducing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and a degree of structural anisotropy of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0237] In the method for reducing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter with a coefficient of variation of 0.5 or less, and a degree of structural anisotropy of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0238] In the method for reducing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and a degree of structural anisotropy of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0239] In the method for suppressing the decrease in the membrane permeability of cell products, the liquid contact surface may also 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, and the liquid contact surface may have a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0240] In the method for suppressing the decrease in the membrane permeability of cell products, the liquid contact surface may also 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 of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0241]

[82] The method for suppressing the decrease in the membrane permeability of cell products according to

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

[0242]

[83] The method for suppressing the decrease in the membrane permeability of cell products according to

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

[0243]

[84] The method for suppressing the decrease in the membrane permeability of cell products according to

[82] or

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

[0244]

[85] The method for suppressing the decrease in the membrane permeability of cell products according to any one of

[82] to

[84] , wherein the hollow fiber membrane comprises a synthetic polymer membrane.

[0245]

[86] The method for suppressing the decrease in the membrane permeability of cell products according to

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

[0246]

[87] The method for suppressing the decrease in the membrane permeability of cell products according to any one of

[81] to

[86] , further comprising the following step: measuring the shear stress based on the viscosity of the culture solution, and controlling the flow rate in the direction parallel to the membrane surface of the culture solution filtered through the porous membrane so that the measured shear stress becomes 4.0 N / m 2 or more.

[0247]

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

[81] to

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

[0248]

[89] The method for suppressing the decrease in the membrane permeability of cell products according to any one of

[81] to

[88] , wherein the product is an antibody.

[0249]

[90] A method for inhibiting the reduction of the membrane permeability of a cell product according to any one of

[81] to

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

[0250]

[91] A cell product manufacturing system, comprising: a culture tank for culturing cells, a porous membrane for filtering the culture solution of the cells to obtain the product of the cells, a pump for transporting the culture solution from the culture tank to the porous membrane, and a control unit for controlling the pump in such a way that the shear stress generated by the flow of the culture solution at the liquid contact surface of the porous membrane is 4.0 N / m 2 or less, the liquid contact surface having at least any one selected from the group consisting of an aperture ratio 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 the liquid contact surface having at least any one selected from the group consisting of a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less.

[0251] In this cell product manufacturing system, the liquid contact surface may also have an aperture ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0252] In this cell product manufacturing system, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0253] In this cell product manufacturing system, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0254] In this cell product manufacturing system, the liquid contact surface may also have an aperture ratio of 57.5% or less and a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0255] In this cell product manufacturing system, the liquid contact surface may also have an aperture ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0256] In this cell product manufacturing system, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0257] In the manufacturing system of the cell product, the liquid contact surface may also 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 diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0258] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less.

[0259] In the manufacturing system of the cell product, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less.

[0260] In the manufacturing system of the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less.

[0261] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less.

[0262] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less.

[0263] In the manufacturing system of the cell product, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less.

[0264] In the manufacturing system of the cell product, the liquid contact surface may also 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 diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less.

[0265] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less.

[0266] In the manufacturing system of the cell product, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less.

[0267] In the production system of the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less.

[0268] In the production system of the cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less.

[0269] In the production system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less.

[0270] In the production system of the cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less.

[0271] In the production system of the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less.

[0272]

[92] In the production system of the cell product according to

[91] , the porous membrane has at least any one selected from the group consisting of a maximum value / minimum value of an average pore diameter of 1 μm or more on the liquid contact surface and an average pore diameter in the membrane thickness direction of 3 or more.

[0273] In the production system of the cell product, the porous membrane may have an average pore diameter of 1 μm or more on the liquid contact surface.

[0274] In the production system of the cell product, the porous membrane may have a maximum value / minimum value of an average pore diameter in the membrane thickness direction of 3 or more.

[0275] In the production system of the cell product, the porous membrane may have an average pore diameter of 1 μm or more on the liquid contact surface and a maximum value / minimum value of an average pore diameter in the membrane thickness direction of 3 or more.

[0276]

[93] The production system of the cell product according to

[91] , wherein the porous membrane has at least any one selected from the group consisting of an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0277] In the production system of the cell product, the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0278] In the production system of the cell product, the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0279] In the production system of the cell product, the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0280]

[94] The production system of the cell product according to

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

[0281]

[95] The production system of the cell product according to

[94] , wherein the hollow fiber membrane has an inclined structure in which the average pore diameter becomes smaller from the primary side to the secondary side in the membrane thickness direction.

[0282]

[96] The production system of the cell product according to

[94] or

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

[0283]

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

[94] to

[96] , wherein the hollow fiber membrane comprises a synthetic polymer membrane.

[0284]

[98] The production system of the cell product according to

[97] , wherein the synthetic polymer is polysulfone.

[0285]

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

[94] to

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

[0286]

[100] The production system of the cell product according to

[92] or any one of

[94] to

[99] , wherein the density of the cells contained in the culture solution to be filtered is 5×10 7 cells / mL or less.

[0287]

[101] The production system of the cell product according to

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

[0288]

[102] The manufacturing system of the cell product according to

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

[0289]

[103] The manufacturing system of the cell product according to

[101] or

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

[0290]

[104] The manufacturing system of the cell product according to any one of

[101] to

[103] , wherein the hollow fiber membrane comprises a synthetic polymer membrane.

[0291]

[105] The manufacturing system of the cell product according to

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

[0292]

[106] The manufacturing system of the cell product according to

[93] or any one of

[101] to

[105] , wherein the density of the cells contained in the culture solution to be filtered is 8×10 7 cells / mL or more.

[0293]

[107] The manufacturing system of the cell product according to any one of

[91] to

[106] , wherein the control unit measures the shear stress based on the viscosity of the culture solution, and controls the flow velocity in the direction parallel to the membrane surface of the culture solution filtered through the porous membrane so that the measured shear stress becomes 4.0 N / m 2 or less.

[0294]

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

[91] to

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

[0295]

[109] The manufacturing system of the cell product 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.

[0296]

[110] The manufacturing system of the cell product according to any one of

[91] to

[109] , wherein the product is an antibody.

[0297]

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

[91] to

[110] , wherein the culture tank performs perfusion culture of cells.

[0298]

[112] A manufacturing system for a cell product, comprising: a culture tank for culturing cells, a porous membrane for filtering the culture solution of the cells to obtain the product of the cells, a pump for transporting the culture solution from the culture tank to the porous membrane, and a control unit for controlling the pump such that the shear stress generated by the flow of the culture solution at the liquid contact surface of the porous membrane is 4.0 N / m 2 or more, the liquid contact surface having at least any one selected from the group consisting of an opening ratio 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 the liquid contact surface having at least any one selected from the group consisting of a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pore of 1.8 or more.

[0299] In this manufacturing system for a cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or less.

[0300] In this manufacturing system for a cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or less.

[0301] In this manufacturing system for a cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or less.

[0302] In this manufacturing system for a cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or less.

[0303] In this manufacturing system for a cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or less.

[0304] In this manufacturing system for a cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or less.

[0305] In this manufacturing system for a cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface may have a structural anisotropy degree of 0.97 or less.

[0306] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a major axis / minor axis of the pores of 1.8 or more.

[0307] In the manufacturing system of the cell product, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less and a major axis / minor axis of the pores of 1.8 or more.

[0308] In the manufacturing system of the cell product, the liquid contact surface may also have a pore size / fiber diameter of 1.3 or less and a major axis / minor axis of the pores of 1.8 or more.

[0309] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and a major axis / minor axis of the pores of 1.8 or more.

[0310] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size / fiber diameter of 1.3 or less, and a major axis / minor axis of the pores of 1.8 or more.

[0311] In the manufacturing system of the cell product, the liquid contact surface may also 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, and a major axis / minor axis of the pores of 1.8 or more.

[0312] In the manufacturing system of the cell product, the liquid contact surface may also 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 of 1.3 or less, and a major axis / minor axis of the pores of 1.8 or more.

[0313] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0314] In the manufacturing system of the cell product, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0315] In the manufacturing system of the cell product, the liquid contact surface may also have a pore size / fiber diameter of 1.3 or less, and a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0316] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, and a structure anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0317] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and a structure anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0318] In the manufacturing system of the cell product, the liquid contact surface may also 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 structure anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0319] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio 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 structure anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0320]

[113] The manufacturing system of the cell product according to

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

[0321]

[114] The manufacturing system of the cell product according to

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

[0322]

[115] The manufacturing system of the cell product according to

[113] or

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

[0323]

[116] The manufacturing system of the cell product according to any one of

[113] to

[115] , wherein the hollow fiber membrane comprises a synthetic polymer membrane.

[0324]

[117] The manufacturing system of the cell product according to

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

[0325]

[118] The manufacturing system of the cell product according to any one of

[112] to

[117] , wherein the control unit measures the shear stress based on the viscosity of the culture solution, and controls the flow rate of the culture solution filtered through the porous membrane in the direction parallel to the membrane surface in such a way that the measured shear stress becomes 4.0 N / m 2 or more.

[0326]

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

[112] to

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

[0327]

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

[112] to

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

[0328]

[121] The manufacturing system of the cell product according to any one of

[112] to

[120] , wherein the product is an antibody.

[0329]

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

[112] to

[121] , wherein the culture tank performs perfusion culture of cells.

[0330]

[123] A purification system of a cell product, comprising: a culture tank for culturing cells, a porous membrane for filtering the culture solution of the cells to purify the cell product, a pump for transporting the culture solution from the culture tank to the porous membrane, and a control unit for controlling the pump in such a way that the shear stress generated by the flow of the culture solution at the liquid contact surface of the porous membrane becomes 4.0 N / m 2 or less, the liquid contact surface has at least any one selected from the group consisting of an aperture ratio 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 the liquid contact surface has at least any one selected from the group consisting of a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less.

[0331] In this purification system of the cell product, the liquid contact surface may have an aperture ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0332] In this purification system of the cell product, the liquid contact surface may have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0333] In this purification system of the cell product, the liquid contact surface may have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0334] In this purification system of the cell product, the liquid contact surface may have an aperture ratio of 57.5% or less and a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0335] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, a pore diameter / fiber diameter of 1.3 or less, and a structural anisotropy degree of 0.97 or more and 1.03 or less.

[0336] In the purification system of the cell product, the liquid contact surface may also 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 degree of 0.97 or more and 1.03 or less.

[0337] In the purification system of the cell product, the liquid contact surface may also have an opening ratio 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 structural anisotropy degree of 0.97 or more and 1.03 or less.

[0338] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and a major axis / minor axis of the pores of 1.8 or less.

[0339] In the purification system of the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and a major axis / minor axis of the pores of 1.8 or less.

[0340] In the purification system of the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and a major axis / minor axis of the pores of 1.8 or less.

[0341] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter with a coefficient of variation of 0.5 or less, and a major axis / minor axis of the pores of 1.8 or less.

[0342] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and a major axis / minor axis of the pores of 1.8 or less.

[0343] In the purification system of the cell product, the liquid contact surface may also 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 major axis / minor axis of the pores of 1.8 or less.

[0344] In the purification system of the cell product, the liquid contact surface may also 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 diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a major axis / minor axis of the pore of 1.8 or less.

[0345] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and a major axis / minor axis of the pore of 1.8 or less.

[0346] In the purification system of the cell product, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and a major axis / minor axis of the pore of 1.8 or less.

[0347] In the purification system of the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and a major axis / minor axis of the pore of 1.8 or less.

[0348] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and a major axis / minor axis of the pore of 1.8 or less.

[0349] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and a major axis / minor axis of the pore of 1.8 or less.

[0350] In the purification system of the cell product, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and a major axis / minor axis of the pore of 1.8 or less.

[0351] In the purification system of the cell product, the liquid contact surface may also 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 diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and a major axis / minor axis of the pore of 1.8 or less.

[0352]

[124] The purification system of the cell product according to

[123] , wherein the porous membrane has at least any one selected from the group consisting of an average pore diameter of 1 μm or more on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 3 or more.

[0353] In the purification system of the cell product, the porous membrane may have an average pore diameter of 1 μm or more on the liquid contact surface.

[0354] In the purification system of the cell product, the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 3 or more.

[0355] In the purification system of the cell product, the porous membrane may have an average pore diameter of 1 μm or more on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 3 or more.

[0356]

[125] The purification system of the cell product according to

[123] , wherein the porous membrane has at least any one selected from the group consisting of an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0357] In the purification system of the cell product, the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0358] In the purification system of the cell product, the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0359] In the purification system of the cell product, the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0360]

[126] The purification system of the cell product according to

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

[0361]

[127] The purification system of the cell product according to

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

[0362]

[128] The purification system of the cell product according to

[126] or

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

[0363]

[129] The purification system of the cell product according to any one of

[126] to

[128] , wherein the hollow fiber membrane comprises a synthetic polymer membrane.

[0364]

[130] The purification system of the cell product according to

[129] , wherein the synthetic polymer is polysulfone.

[0365]

[131] The purification system of the cell product according to any one of

[126] to

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

[0366]

[132] The purification system of the cell product according to

[124] or any one of

[126] to

[131] , wherein the density of the cells contained in the culture solution to be filtered is 5×10 7 cells / mL or less.

[0367]

[133] The purification system of the cell product according to

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

[0368]

[134] The purification system of the cell product according to

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

[0369]

[135] The purification system of the cell product according to

[133] or

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

[0370]

[136] The purification system of the cell product according to any one of

[133] to

[135] , wherein the hollow fiber membrane comprises a synthetic polymer membrane.

[0371]

[137] The purification system of the cell product according to

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

[0372]

[138] The purification system of the cell product according to

[125] or any one of

[133] to

[137] , wherein the density of the cells contained in the culture solution to be filtered is 8×10 7 cells / mL or more.

[0373]

[139] The purification system of the cell product according to any one of

[123] to

[138] , wherein the control unit measures the shear stress based on the viscosity of the culture solution, and controls the flow velocity of the culture solution filtered through the porous membrane in the direction parallel to the membrane surface so that the measured shear stress becomes 4.0 N / m 2 or less.

[0374]

[140] The purification system of the cell product according to any one of

[123] to

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

[0375]

[141] The purification system of the cell product according to any one of

[123] to

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

[0376]

[142] The purification system of the cell product according to any one of

[123] to

[141] , wherein the product is an antibody.

[0377]

[143] The purification system of the cell product according to any one of

[123] to

[142] , wherein the culture tank performs perfusion culture of cells.

[0378]

[144] A purification system of a cell product, comprising: a culture tank for culturing cells, a porous membrane for filtering the culture solution of the cells to purify the cell product, a pump for transporting the culture solution from the culture tank to the porous membrane, and a control unit for controlling the pump in such a manner that the shear stress generated by the flow of the culture solution at the liquid contact surface of the porous membrane becomes 4.0 N / m 2 or more, the liquid contact surface having at least any one selected from the group consisting of an opening ratio 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 the liquid contact surface having at least any one selected from the group consisting of a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pore of 1.8 or more.

[0379] In this purification system of the cell product, it is also possible that the liquid contact surface has an opening ratio of 57.5% or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or less.

[0380] In this purification system of the cell product, it is also possible that the liquid contact surface has a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or less.

[0381] In this purification system of the cell product, it is also possible that the liquid contact surface has a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or less.

[0382] In this purification system of the cell product, it is also possible that the liquid contact surface has 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 contact surface has a structural anisotropy degree of 0.97 or less.

[0383] In this purification system of the cell product, it is also possible that the liquid contact surface has an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or less.

[0384] In the purification system of the cell product, the liquid contact surface may also 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, and the liquid contact surface has a structural anisotropy degree of 0.97 or less.

[0385] In the purification system of the cell product, the liquid contact surface may also 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 of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or less.

[0386] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or more.

[0387] In the purification system of the cell product, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or more.

[0388] In the purification system of the cell product, the liquid contact surface may also have a pore size / fiber diameter of 1.3 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or more.

[0389] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or more.

[0390] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size / fiber diameter of 1.3 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or more.

[0391] In the purification system of the cell product, the liquid contact surface may also 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, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or more.

[0392] In the purification system of the cell product, the liquid contact surface may also 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 of 1.3 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or more.

[0393] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more.

[0394] In the purification system of the cell product, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pore of 1.8 or more.

[0395] In the purification system of the cell product, the liquid contact surface may also have a pore size / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pore of 1.8 or more.

[0396] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pore of 1.8 or more.

[0397] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pore of 1.8 or more.

[0398] In the purification system of the cell product, the liquid contact surface may also 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, and the liquid contact surface has a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pore of 1.8 or more.

[0399] In the purification system of the cell product, the liquid contact surface may also 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 of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pore of 1.8 or more.

[0400]

[145] The purification system of the cell product according to

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

[0401]

[146] The purification system of the cell product according to

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

[0402]

[147] The purification system of the cell product according to

[145] or

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

[0403]

[148] The purification system of the cell product according to any one of

[145] to

[147] , wherein the hollow fiber membrane comprises a synthetic polymer membrane.

[0404]

[149] The purification system for cell products according to

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

[0405]

[150] The purification system for cell products according to any one of

[144] to

[149] , wherein the control unit measures the shear stress based on the viscosity of the culture solution, and controls the flow velocity of the culture solution filtered through the porous membrane in the direction parallel to the membrane surface in such a manner that the measured shear stress becomes 4.0 N / m 2 or more.

[0406]

[151] The purification system for cell products according to any one of

[144] to

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

[0407]

[152] The purification system for cell products according to any one of

[144] to

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

[0408]

[153] The purification system for cell products according to any one of

[144] to

[152] , wherein the product is an antibody.

[0409]

[154] The purification system for cell products according to any one of

[144] to

[153] , wherein the culture tank performs perfusion culture of cells.

[0410]

[155] A method for producing a cell product, comprising a step of obtaining a cell product by filtering a culture solution of cells through a porous membrane, the porous membrane having a liquid contact surface, the liquid contact surface having at least any one selected from the group consisting of an opening ratio 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 the liquid contact surface having at least any one selected from the group consisting of a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane having at least any one selected from the group consisting of an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less, and the density of cells contained in the culture solution to be filtered is 8×10 7 cells / mL or more.

[0411] In this method for producing a cell product, the liquid contact surface may have an opening ratio of 57.5% or less, the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0412] In the method for manufacturing the cell product, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0413] In the method for manufacturing the cell product, the liquid contact surface may also have a pore size / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0414] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0415] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0416] In the method for manufacturing the cell product, the liquid contact surface may also 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, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0417] In the method for manufacturing the cell product, the liquid contact surface may also 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 of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0418] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a major axis / minor axis of the pore of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0419] In the method for manufacturing the cell product, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a major axis / minor axis of the pore of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0420] In the method for manufacturing the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0421] In the method for manufacturing the cell product, the liquid contact surface may also 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 contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0422] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0423] In the method for manufacturing the cell product, the liquid contact surface may also 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 contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0424] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0425] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0426] In the method for manufacturing the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0427] In the method for manufacturing the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0428] In the method for manufacturing the cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0429] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0430] In the method for manufacturing the cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0431] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0432] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0433] In the method for manufacturing the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0434] In the method for manufacturing the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0435] In the method for manufacturing the cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0436] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0437] In the method for manufacturing the cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0438] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0439] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0440] In the method for manufacturing the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0441] In the method for manufacturing the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0442] In the method for manufacturing the cell product, the liquid contact surface may also have an aperture ratio of 57.5% or less and a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0443] In the method for manufacturing the cell product, the liquid contact surface may also have an aperture ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0444] In the method for manufacturing the cell product, the liquid contact surface may also 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 contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0445] In the method for manufacturing the cell product, the liquid contact surface may also have an aperture ratio 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 the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0446] In the method for manufacturing the cell product, the liquid contact surface may also have an aperture ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0447] In the method for manufacturing the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0448] In the method for manufacturing the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0449] In the method for manufacturing the cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0450] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0451] In the method for manufacturing the cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0452] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0453] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0454] In the method for manufacturing the cell product, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0455] In the method for manufacturing the cell product, the liquid contact surface may also have a pore size / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0456] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0457] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0458] In the method for manufacturing the cell product, the liquid contact surface may also 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, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0459] In the method for manufacturing the cell product, the liquid contact surface may also 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 of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0460] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0461] In the method for manufacturing the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0462] In the method for manufacturing the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0463] In the method for manufacturing the cell product, the liquid contact surface may also 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 contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0464] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0465] In the method for manufacturing the cell product, the liquid contact surface may also 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 contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0466] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0467] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0468] In the method for manufacturing the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0469] In the method for manufacturing the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0470] In the method for manufacturing the cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0471] In the method for manufacturing the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0472] In the method for producing the cell product, the liquid contact surface may also 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, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore size of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0473] In the method for producing the cell product, the liquid contact surface may also 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 of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore size of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0474]

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

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

[0475]

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

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

[0476]

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

[156] or

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

[0477]

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

[156] to

[158] , wherein the hollow fiber membrane comprises a synthetic polymer membrane.

[0478]

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

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

[0479]

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

[155] to

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

[0480]

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

[155] to

[161] , wherein the product is an antibody.

[0481]

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

[155] to

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

[0482]

[164] A method for purifying a cell product, which includes the step of purifying the cell product by filtering a cell culture solution with a porous membrane. The porous membrane has a liquid contact surface, and the liquid contact surface has at least any one selected from the group consisting of an opening ratio 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 the liquid contact surface has at least any one selected from the group consisting of a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less. And the porous membrane has at least any one selected from the group consisting of an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less. And the density of cells contained in the culture solution to be filtered is 8×10 7 cells / mL or more.

[0483] In this method for purifying a cell product, it is also possible that the liquid contact surface has an opening ratio of 57.5% or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface.

[0484] In this method for purifying a cell product, it is also possible that the liquid contact surface has a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface.

[0485] In this method for purifying a cell product, it is also possible that the liquid contact surface has a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface.

[0486] In this method for purifying a cell product, it is also possible that the liquid contact surface has 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 contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface.

[0487] In this method for purifying a cell product, it is also possible that the liquid contact surface has an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface.

[0488] In the method for purifying the cell product, the liquid contact surface may also 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, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0489] In the method for purifying the cell product, the liquid contact surface may also 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 of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0490] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0491] In the method for purifying the cell product, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0492] In the method for purifying the cell product, the liquid contact surface may also have a pore size / fiber diameter of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0493] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0494] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size / fiber diameter of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0495] In the method for purifying the cell product, the liquid contact surface may also 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, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0496] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0497] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0498] In the method for purifying the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0499] In the method for purifying the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0500] In the method for purifying the cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0501] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0502] In the method for purifying the cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0503] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0504] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0505] In the method for purifying the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0506] In the method for purifying the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0507] In the method for purifying the cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0508] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0509] In the method for purifying the cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0510] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0511] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0512] In the method for purifying the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0513] In the method for purifying the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0514] In the method for purifying the cell product, the liquid contact surface may also 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 contact surface has a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0515] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0516] In the method for purifying the cell product, the liquid contact surface may also 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 contact surface has a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0517] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0518] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0519] In the method for purifying the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0520] In the method for purifying the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0521] In the method for purifying the cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0522] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0523] In the method for purifying the cell product, the liquid contact surface may also 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, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0524] In the method for purifying the cell product, the liquid contact surface may also 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 of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0525] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore size of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0526] In the method for purifying the cell product, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore size of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0527] In the method for purifying the cell product, the liquid contact surface may also have a pore size / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore size of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0528] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore size of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0529] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0530] In the method for purifying the cell product, the liquid contact surface may also 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 contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0531] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0532] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0533] In the method for purifying the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0534] In the method for purifying the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0535] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0536] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0537] In the method for purifying the cell product, the liquid contact surface may also 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 major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0538] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio 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 major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0539] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0540] In the method for purifying the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0541] In the method for purifying the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0542] In the method for purifying the cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0543] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0544] In the method for purifying the cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0545] In the method for purifying the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0546]

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

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

[0547]

[166] The purification method of the cell product according to

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

[0548]

[167] The purification method of the cell product according to

[165] or

[166] , wherein the rejection pore diameter of the pores of the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

[0549]

[168] The purification method of the cell product according to any one of

[165] to

[167] , wherein the hollow fiber membrane comprises a synthetic polymer membrane.

[0550]

[169] The purification method of the cell product according to

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

[0551]

[170] The purification method of the cell product according to any one of

[165] to

[169] , wherein the culture solution not filtered by the hollow fiber membrane is returned to the cell culture tank.

[0552]

[171] The purification method of the cell product according to any one of

[164] to

[170] , wherein the product is an antibody.

[0553]

[172] The purification method of the cell product according to any one of

[164] to

[171] , wherein the cells are subjected to perfusion culture.

[0554]

[173] A method for inhibiting the reduction of the membrane permeability of a cell product, which includes the step of filtering the culture solution of cells with a porous membrane to obtain the cell product, the porous membrane having a liquid contact surface, the liquid contact surface having at least any one selected from the group consisting of an opening ratio 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 the liquid contact surface having at least any one selected from the group consisting of a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane having at least any one selected from the group consisting of an average pore diameter of 10 μm or less of the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less, and setting the density of the cells contained in the culture solution to be filtered as 8×10 7 cells / mL or more, thereby inhibiting the reduction of the membrane permeability of the cell product.

[0555] In this method for inhibiting the reduction of the membrane permeability of the cell product, it is also possible that the liquid contact surface has an opening ratio of 57.5% or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less of the liquid contact surface.

[0556] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0557] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore size / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0558] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0559] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0560] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0561] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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 of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0562] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface.

[0563] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less of the liquid contact surface.

[0564] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore size / fiber diameter of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less of the liquid contact surface.

[0565] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an aperture ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less of the liquid contact surface.

[0566] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an aperture ratio of 57.5% or less and a pore size / fiber diameter of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less of the liquid contact surface.

[0567] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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, and the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less of the liquid contact surface.

[0568] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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 diameter of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less of the liquid contact surface.

[0569] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an aperture ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less of the liquid contact surface.

[0570] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has an average pore size of 10 μm or less of the liquid contact surface.

[0571] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore size / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has an average pore size of 10 μm or less of the liquid contact surface.

[0572] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an aperture ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has an average pore size of 10 μm or less of the liquid contact surface.

[0573] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an aperture ratio of 57.5% or less and a pore size / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has an average pore size of 10 μm or less of the liquid contact surface.

[0574] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has an average pore size of 10 μm or less of the liquid contact surface.

[0575] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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 diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has an average pore size of 10 μm or less of the liquid contact surface.

[0576] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0577] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0578] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0579] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0580] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0581] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0582] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio 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 the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0583] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0584] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0585] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0586] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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 contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0587] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0588] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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 contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0589] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio 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 the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0590] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0591] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0592] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0593] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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 contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0594] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0595] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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 contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0596] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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 of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0597] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0598] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0599] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore size / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0600] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0601] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0602] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0603] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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 of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0604] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0605] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0606] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore size / fiber diameter of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0607] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0608] In this method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less, a pore diameter / fiber diameter of 1.3 or less, and an aspect ratio of the pores of 1.8 or less. The porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0609] In this method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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 an aspect ratio of the pores of 1.8 or less. The porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0610] In this method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio 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 an aspect ratio of the pores of 1.8 or less. The porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0611] In this method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less, and a structural anisotropy degree of 0.97 or more and 1.03 or less, and an aspect ratio of the pores of 1.8 or less. The porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0612] In this method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and a structural anisotropy degree of 0.97 or more and 1.03 or less, and an aspect ratio of the pores of 1.8 or less. The porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0613] In this method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and a structural anisotropy degree of 0.97 or more and 1.03 or less, and an aspect ratio of the pores of 1.8 or less. The porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0614] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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 contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0615] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0616] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also 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 contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0617] In the method for suppressing the reduction in the membrane permeability of cell products, the liquid contact surface may also have an opening ratio 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 the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0618]

[174] The method for suppressing the reduction in the membrane permeability of cell products according to

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

[0619]

[175] The method for suppressing the reduction in the membrane permeability of cell products according to

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

[0620]

[176] The method for suppressing the reduction in the membrane permeability of cell products according to

[174] or

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

[0621]

[177] The method for suppressing the reduction in the membrane permeability of a cell product according to any one of

[174] to

[176] , wherein the hollow fiber membrane comprises a synthetic polymer membrane.

[0622]

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

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

[0623]

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

[174] to

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

[0624]

[180] The method for suppressing the reduction in the membrane permeability of a cell product according to any one of

[173] to

[179] , wherein the product is an antibody.

[0625]

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

[173] to

[180] , wherein the cells are subjected to perfusion culture.

[0626]

[182] A cell product manufacturing system, comprising: a culture tank for culturing cells, a porous membrane for filtering the culture medium of the cells to obtain the product of the cells, and a pump for transporting the culture medium from the culture tank to the porous membrane. The liquid contact surface of the porous membrane has at least any one selected from the group consisting of an aperture ratio 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 the liquid contact surface has at least any one selected from the group consisting of a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less. And the porous membrane has at least any one selected from the group consisting of an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less. And the density of the cells contained in the culture medium to be filtered is 8 × 10 7 cells / mL or more.

[0627] In this cell product manufacturing system, the liquid contact surface may have an aperture ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0628] In this cell product manufacturing system, the liquid contact surface may have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface.

[0629] In the manufacturing system of the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore diameter of 10 μm or less of the liquid contact surface.

[0630] In the manufacturing system of the cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore diameter of 10 μm or less of the liquid contact surface.

[0631] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore diameter of 10 μm or less of the liquid contact surface.

[0632] In the manufacturing system of the cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore diameter of 10 μm or less of the liquid contact surface.

[0633] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore diameter of 10 μm or less of the liquid contact surface.

[0634] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less of the liquid contact surface.

[0635] In the manufacturing system of the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less of the liquid contact surface.

[0636] In the manufacturing system of the cell product, it is also possible that the liquid contact surface has a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less of the liquid contact surface.

[0637] In the manufacturing system of the cell product, it is also possible that the liquid contact surface has 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 contact surface has a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less of the liquid contact surface.

[0638] In the manufacturing system of the cell product, it is also possible that the liquid contact surface has an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less of the liquid contact surface.

[0639] In the manufacturing system of the cell product, it is also possible that the liquid contact surface has 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 contact surface has a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less of the liquid contact surface.

[0640] In the manufacturing system of the cell product, it is also possible that the liquid contact surface has an opening ratio 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 the liquid contact surface has a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less of the liquid contact surface.

[0641] In the manufacturing system of the cell product, it is also possible that the liquid contact surface has an opening ratio of 57.5% or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less of the liquid contact surface.

[0642] In the manufacturing system of the cell product, it is also possible that the liquid contact surface has a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less of the liquid contact surface.

[0643] In the manufacturing system of the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less of the liquid contact surface.

[0644] In the manufacturing system of the cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less of the liquid contact surface.

[0645] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less of the liquid contact surface.

[0646] In the manufacturing system of the cell product, the liquid contact surface may also 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 contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less of the liquid contact surface.

[0647] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less of the liquid contact surface.

[0648] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0649] In the manufacturing system of the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0650] In the manufacturing system of the cell product, it is also possible that the liquid contact surface has a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0651] In the manufacturing system of the cell product, it is also possible that the liquid contact surface has 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 contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0652] In the manufacturing system of the cell product, it is also possible that the liquid contact surface has an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0653] In the manufacturing system of the cell product, it is also possible that the liquid contact surface has 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 contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0654] In the manufacturing system of the cell product, it is also possible that the liquid contact surface has an opening ratio 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 the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0655] In the manufacturing system of the cell product, it is also possible that the liquid contact surface has an opening ratio of 57.5% or less, and the liquid contact surface has a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0656] In the manufacturing system of the cell product, it is also possible that the liquid contact surface has a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface has a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0657] In the manufacturing system of the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0658] In the manufacturing system of the cell product, the liquid contact surface may also 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 contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0659] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0660] In the manufacturing system of the cell product, the liquid contact surface may also 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 contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0661] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0662] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0663] In the manufacturing system of the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0664] In the manufacturing system of the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0665] In the manufacturing system of the cell product, the liquid contact surface may also 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 contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0666] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0667] In the manufacturing system of the cell product, the liquid contact surface may also 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 contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0668] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0669] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0670] In the manufacturing system of the cell product, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore size of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0671] In the manufacturing system of the cell product, the liquid contact surface has a pore size / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore size of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0672] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore size of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0673] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore size of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0674] In the manufacturing system of the cell product, the liquid contact surface may also 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, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore size of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0675] In the manufacturing system of the cell product, the liquid contact surface may also 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 of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore size of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0676] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0677] In the manufacturing system of the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0678] In the manufacturing system of the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0679] In the manufacturing system of the cell product, the liquid contact surface may also 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 contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0680] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0681] In the manufacturing system of the cell product, the liquid contact surface may also 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 contact surface may have a major axis / minor axis of pores of 1.8 or less, and the porous membrane may have an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0682] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0683] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0684] In the manufacturing system of the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0685] In the manufacturing system of the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0686] In the manufacturing system of the cell product, the liquid contact surface may also 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 contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0687] In the manufacturing system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0688] In the production system of the cell product, the liquid contact surface may also 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, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore size of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0689] In the production system of the cell product, the liquid contact surface may also 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 of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore size of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0690]

[183] The production system of the cell product according to

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

[0691]

[184] The production system of the cell product according to

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

[0692]

[185] The production system of the cell product according to

[183] or

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

[0693]

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

[183] to

[185] , wherein the hollow fiber membrane comprises a synthetic polymer membrane.

[0694]

[187] The production system of the cell product according to

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

[0695]

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

[182] to

[187] further comprises a control unit that receives an input of viscosity data of the culture medium.

[0696]

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

[182] to

[188] further comprises a flow path for returning the culture medium that has not been filtered by the hollow fiber membrane to the culture tank.

[0697]

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

[182] to

[189] , wherein the product is an antibody.

[0698]

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

[182] to

[190] , wherein the culture tank performs perfusion culture of cells.

[0699]

[192] A purification system of a cell product, comprising: a culture tank for culturing cells, a porous membrane for filtering the culture solution of the cells to purify the cell product, and a pump for transporting the culture solution from the culture tank to the porous membrane. The liquid contact surface of the porous membrane has at least any one selected from the group consisting of an opening ratio 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 the liquid contact surface has at least any one selected from the group consisting of a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less. And the porous membrane has at least any one selected from the group consisting of an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less. And the density of the cells contained in the culture solution to be filtered is 8×10 7 cells / mL or more.

[0700] In this purification system of the cell product, it is also possible that the liquid contact surface has an opening ratio of 57.5% or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface.

[0701] In this purification system of the cell product, it is also possible that the liquid contact surface has a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface.

[0702] In this purification system of the cell product, it is also possible that the liquid contact surface has a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface.

[0703] In this purification system of the cell product, it is also possible that the liquid contact surface has 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 contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface.

[0704] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less of the liquid contact surface.

[0705] In the purification system of the cell product, the liquid contact surface may also 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 contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less of the liquid contact surface.

[0706] In the purification system of the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less of the liquid contact surface.

[0707] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less of the liquid contact surface.

[0708] In the purification system of the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface has a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less of the liquid contact surface.

[0709] In the purification system of the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less of the liquid contact surface.

[0710] In the purification system of the cell product, the liquid contact surface may also 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 contact surface has a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less of the liquid contact surface.

[0711] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less of the liquid contact surface.

[0712] In the purification system of the cell product, the liquid contact surface may also 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, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less of the liquid contact surface.

[0713] In the purification system of the cell product, the liquid contact surface may also 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 of 1.3 or less, and the liquid contact surface may have a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less of the liquid contact surface.

[0714] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less of the liquid contact surface.

[0715] In the purification system of the cell product, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less of the liquid contact surface.

[0716] In the purification system of the cell product, the liquid contact surface may also have a pore size / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less of the liquid contact surface.

[0717] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less of the liquid contact surface.

[0718] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size / fiber diameter of 1.3 or less, and the liquid contact surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 μm or less of the liquid contact surface.

[0719] In the purification system of the cell product, it is also possible that the liquid contact surface has a pore size with a coefficient of variation of 0.5 or less and a pore size / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore size of 10 μm or less on the liquid contact surface.

[0720] In the purification system of the cell product, it is also possible that the liquid contact surface has 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 of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore size of 10 μm or less on the liquid contact surface.

[0721] In the purification system of the cell product, it is also possible that the liquid contact surface has an opening ratio of 57.5% or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0722] In the purification system of the cell product, it is also possible that the liquid contact surface has a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0723] In the purification system of the cell product, it is also possible that the liquid contact surface has a pore size / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0724] In the purification system of the cell product, it is also possible that the liquid contact surface has an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0725] In the purification system of the cell product, it is also possible that the liquid contact surface has an opening ratio of 57.5% or less and a pore size / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0726] In the purification system of the cell product, the liquid contact surface may also 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, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0727] In the purification system of the cell product, the liquid contact surface may also 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 of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0728] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0729] In the purification system of the cell product, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0730] In the purification system of the cell product, the liquid contact surface may also have a pore size / fiber diameter of 1.3 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0731] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0732] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size / fiber diameter of 1.3 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has a maximum / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0733] In the purification system of the cell product, the liquid contact surface may also 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, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0734] In the purification system of the cell product, the liquid contact surface may also 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 of 1.3 or less, and the liquid contact surface has a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0735] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0736] In the purification system of the cell product, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0737] In the purification system of the cell product, the liquid contact surface may also have a pore size / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0738] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0739] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0740] In the purification system of the cell product, the liquid contact surface may also 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, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0741] In the purification system of the cell product, the liquid contact surface may also 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 of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0742] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore size of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0743] In the purification system of the cell product, the liquid contact surface may also have a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore size of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0744] In the purification system of the cell product, the liquid contact surface may also have a pore size / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore size of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0745] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore size of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.

[0746] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0747] In the purification system of the cell product, the liquid contact surface may also 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 contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0748] In the purification system of the cell product, the liquid contact surface may also have an opening ratio 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 the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0749] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and the liquid contact surface has a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0750] In the purification system of the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and the liquid contact surface has a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0751] In the purification system of the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0752] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, a pore diameter with a coefficient of variation of 0.5 or less, and a major axis / minor axis of the pores of 1.8 or less. The porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0753] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and a major axis / minor axis of the pores of 1.8 or less. The porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0754] In the purification system of the cell product, the liquid contact surface may also 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 major axis / minor axis of the pores of 1.8 or less. The porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0755] In the purification system of the cell product, the liquid contact surface may also have an opening ratio 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 major axis / minor axis of the pores of 1.8 or less. The porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0756] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less, and a structural anisotropy degree of 0.97 or more and 1.03 or less, and a major axis / minor axis of the pores of 1.8 or less. The porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0757] In the purification system of the cell product, the liquid contact surface may also have a pore diameter with a coefficient of variation of 0.5 or less, and a structural anisotropy degree of 0.97 or more and 1.03 or less, and a major axis / minor axis of the pores of 1.8 or less. The porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0758] In the purification system of the cell product, the liquid contact surface may also have a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0759] In the purification system of the cell product, the liquid contact surface may also 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 contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0760] In the purification system of the cell product, the liquid contact surface may also have an opening ratio of 57.5% or less and a pore diameter / fiber diameter of 1.3 or less, and the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0761] In the purification system of the cell product, the liquid contact surface may also 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 contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0762] In the purification system of the cell product, the liquid contact surface has an opening ratio 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 the liquid contact surface has a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pore of 1.8 or less, and the porous membrane has an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less.

[0763]

[193] The purification system of the cell product according to

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

[0764]

[194] The purification system of the cell product according to

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

[0765]

[195] The purification system of the cell product according to

[193] or

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

[0766]

[196] The purification system of the cell product according to any one of

[193] to

[195] , wherein the hollow fiber membrane comprises a synthetic polymer membrane.

[0767]

[197] The purification system of the cell product according to

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

[0768]

[198] The purification system of the cell product according to any one of

[192] to

[197] , further comprising a control unit that receives an input of viscosity data of the culture solution.

[0769]

[199] The purification system of the cell product according to any one of

[192] to

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

[0770]

[200] The purification system of the cell product according to any one of

[192] to

[199] , wherein the product is an antibody.

[0771]

[201] The purification system of the cell product according to any one of

[192] to

[200] , wherein the culture tank performs perfusion culture of cells.

[0772] Effects of the Invention

[0773] 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 the membrane permeability of a cell product, a production system for a cell product, and a purification system for a cell product, which can suppress a decrease in the permeability of the cell product through a porous membrane. BRIEF DESCRIPTION OF THE DRAWINGS

[0774] Figure 1 is a diagram schematically showing a production system for a cell product according to an embodiment.

[0775] Figure 2 is a diagram showing an example of image processing in the local thickness method according to an embodiment.

[0776] Figure 3 is a diagram showing an example of the maximum circle shown in the local thickness method according to an embodiment.

[0777] Figure 4 is a diagram showing an example of the maximum circle shown in the local thickness method according to an embodiment.

[0778] Figure 5 This is a diagram showing an example of image processing of an embodiment.

[0779] Figure 6 This is a diagram showing an example of image processing when calculating the structural anisotropy degree Z' of the surface of a porous membrane in an embodiment.

[0780] Figure 7 This is a diagram schematically showing the flow velocity distribution and shear stress distribution of a fluid flowing in a hollow portion when the porous membrane of the embodiment is a hollow fiber membrane.

[0781] Figure 8 This is a diagram schematically showing a filter cake layer and blockage in a cross section when the porous membrane of the embodiment is a hollow fiber membrane.

[0782] Figure 9 This is a graph showing the relationship between the shear stress on the liquid contact surface of the hollow fiber membrane of the example and the antibody permeation rate at the time when the filtration volume is 300 L / m 2 at a certain moment.

[0783] Figure 10 This is a graph showing the relationship between the shear stress on the liquid contact surface of the hollow fiber membrane of the example and the transmembrane pressure difference at the time when the filtration volume is 300 L / m 2 at a certain moment.

[0784] Figure 11 This is a graph showing the relationship between the shear stress on the liquid contact surface of the hollow fiber membrane of the example and the antibody permeation rate at the time when the filtration volume is 300 L / m 2 at a certain moment.

[0785] Figure 12 This is a graph showing the relationship between the shear stress on the liquid contact surface of the hollow fiber membrane of the example and the transmembrane pressure difference at the time when the filtration volume is 300 L / m 2 at a certain moment.

[0786] Figure 13 This is a graph showing the relationship between the shear stress on the liquid contact surface of the hollow fiber membrane of the example and the antibody permeation rate at the time when the filtration volume is 300 L / m 2 at a certain moment.

[0787] Figure 14 This is a graph showing the relationship between the shear stress on the liquid contact surface of the hollow fiber membrane of the example and the transmembrane pressure difference at the time when the filtration volume is 300 L / m 2 at a certain moment. Detailed implementation manners

[0788] The following describes in detail the method for implementing the present invention (hereinafter referred to as "the present embodiment"). It should be noted that the present embodiment is for facilitating the understanding of the present invention and is not for a restrictive interpretation of the present invention. The present invention is not limited by the present embodiment and can be implemented with various modifications within its gist.

[0789] Referring to Figure 1 , the method for manufacturing the cell product of the present embodiment includes the step of filtering the culture solution of cells with the porous membrane 112 to obtain the cell product. For example, the culture solution of cells is transported from the culture tank 111 to the porous membrane 112. In order to prevent external bacteria from entering the inside of the culture tank 111, the culture tank 111 may have: a ventilation port having a pore size of 0.2 μm or less, and a filter. The culture tank 111 may be provided with a stirring device 212 for stirring the culture solution in the culture tank 111. The cells are cultured in suspension in the culture solution in the culture tank 111.

[0790] The cells cultured in the culture tank 111 are not particularly limited. The cells may be derived from animals including humans, or may be derived from microorganisms. The cells may be eukaryotic cells or prokaryotic cells. Examples of animals include mammals, reptiles, birds, amphibians, fish, and insects. The cells may be genetically recombinant 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.

[0791] The cells produce products that can be used as drugs, for example, and release them into the culture solution. Examples of products that can be used as drugs include peptides, proteins, and viruses (including virus-like particles). Examples of proteins include antibodies, hormones, cytokines, growth factors, enzymes, and plasma proteins. The proteins may be recombinant proteins.

[0792] The antibody may be a monoclonal antibody or a polyclonal antibody. The antibody may be a human antibody or an antibody protein derived from mammals other than humans, such as cows and mice. Alternatively, the antibody may be a chimeric antibody protein with human IgG and 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, and the remaining constant region is replaced with an immunoglobulin derived from a human. In addition, a humanized antibody refers to an antibody in which the complementarity-determining region (CDR) in the variable region is derived from a non-human organism, and the remaining framework region (FR) is derived from a human. Humanization further reduces the immunogenicity compared to chimeric antibodies.

[0793] By filtering the cell-containing culture solution using the porous membrane 112, the cells in the culture solution are removed, and the cell products in the culture solution pass through the porous membrane 112 and are purified. In the porous membrane 112, the surface in contact with the filtered culture solution is referred to as the liquid contact surface. The shape of the porous membrane 112 is not particularly limited. Examples of the porous membrane include a hollow fiber membrane, a flat membrane, and a tubular membrane, etc. Hereinafter, an example in which the porous membrane 112 is a hollow fiber membrane will be described. The liquid contact surface of the hollow fiber membrane where the cell culture solution is supplied is referred to as the primary side of the hollow fiber membrane. In addition, the surface through which the permeate flowing through the hollow fiber membrane flows out is referred to as 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 peripheral surface, the inner peripheral surface of the hollow fiber membrane becomes the primary side, and the outer peripheral surface of the hollow fiber membrane becomes the secondary side. In an embodiment in which the cell culture solution to be filtered is supplied to the outer peripheral surface, the outer peripheral surface of the hollow fiber membrane becomes the primary side, and the inner peripheral surface of the hollow fiber membrane becomes the secondary side.

[0794] The filtration method of the porous membrane 112 can be a tangential flow filtration (TFF) method. The tangential flow filtration method refers to a filtration method in which the culture solution flows along a direction parallel to the primary side surface of the hollow fiber membrane on the primary side surface of the hollow fiber membrane. The tangential flow filtration method includes an alternating tangential flow filtration (ATF) method. In the present embodiment, when simply referred to as the tangential flow filtration (TFF) method, it sometimes refers to a filtration method in which the culture solution flows unidirectionally on the primary side surface of the hollow fiber membrane. The alternating tangential flow filtration (ATF) method refers to a filtration method in which the culture solution reciprocates on the primary side surface of the hollow fiber membrane.

[0795] Between the culture tank 111 and the porous membrane 112, there are arranged a flow path 113 for transporting the culture solution in the culture tank 111 to the porous membrane 112 and a flow path 114 for returning the culture solution that passes through the hollow part instead of passing through the pore part of the porous membrane 112 and thus is not filtered by the porous membrane 112 but passes through the porous membrane 112 to the culture tank 111. The culture solution flowing in the flow path 113 may contain cells and cell products. The culture solution flowing in the flow path 114 that is directly passed without being filtered by the porous membrane 112 may contain cells and cell products. In addition, the porous membrane 112 is connected to a flow path 115 for recovering the culture solution that has passed through the pore part of the porous membrane 112 and has been filtered. The culture solution filtered by the porous membrane 112 flowing in the flow path 115 may contain cell products. The culture solution filtered by the porous membrane 112 is, for example, recovered into the container 201. The container 201 can be aseptically connected to the flow path 115. The flow path 115 through which the culture solution filtered by the porous membrane 112 flows can be directly connected to, for example, a column for the following purification process.

[0796] The flow path 113 is provided with, for example, a pump 123 for delivering the culture solution in the culture tank 111 to the porous membrane 112. Examples of the pump include a diaphragm pump, a tube pump, a centrifugal pump, and a rotary pump, but are not limited to these. 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 any one of the flow velocity and flow rate of the culture solution flowing in the flow path 113. The flow path 113 may be provided with a thermometer for measuring the temperature of the culture solution flowing in the flow path 113. The flow path 113 may be provided with a sampling section for sampling the culture solution flowing in the flow path 113. The sampling section is closed except during sampling.

[0797] The flow path 114 may be provided with a pump for delivering the culture solution that has passed through the hollow portion without passing through the pore portion of the porous membrane 112 and has not been filtered by the porous membrane 112 to the culture tank 111. It should be noted that the pump may be provided in both the flow path 113 and the flow path 114, or may be provided in either one of them. The flow path 114 may be provided with a pressure gauge 134 for measuring 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 for measuring at least any one of the flow velocity and flow rate of the culture solution flowing in the flow path 114. The flow path 114 may be provided with a thermometer for measuring the temperature of the culture solution flowing in the flow path 114. The flow path 114 may be provided with a sampling section for sampling the culture solution flowing in the flow path 114. The sampling section is closed except during sampling.

[0798] The flow path 115 is provided with, for example, a pump 125 for delivering the culture solution that has passed through the pore portion of the porous membrane 112 and has been filtered by 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 any one of the flow velocity and flow rate of the culture solution flowing in the flow path 115. The flow path 115 may be provided with a sampling section for sampling the culture solution flowing in the flow path 115. The sampling section is closed except during sampling.

[0799] The culture tank 111 and the porous membrane 112 constitute at least a part of the path for circulating the culture solution. In addition, the flow paths 113 and 114 constitute at least a part of the path for circulating the culture solution.

[0800] The culture tank 111 may be connected to a flow path 116 for supplying a culture solution to the culture tank 111. The flow path 116 is connected, for example, to a culture solution tank 216 that houses the culture solution. The flow path 116 is provided, for example, with a pump 126 for transporting the culture solution to the culture tank 111. For example, the pumps 125 and 126 are controlled such that the amount of the culture solution that has been filtered by the porous membrane 112 and does not return to the culture tank 111 is the same as the amount of the culture solution supplied to the culture tank 111. This control can be performed as follows: observing the liquid level height using a liquid level sensor (level sensor) provided in the culture tank 111 and keeping the liquid level height fixed; or measuring the total weight of the culture tank 111 including the culture solution and keeping the weight fixed.

[0801] The culture tank 111 may be connected to a flow path 117 for supplying air containing carbon dioxide to the culture tank 111. The flow path 117 may be connected, for example, to a container 217 that houses the air containing carbon dioxide. In addition, the culture tank 111 may be connected to a flow path 118 for supplying oxygen to the culture tank 111. The flow path 118 may be connected, for example, to a container 218 that houses oxygen.

[0802] The culture tank 111 may be connected to a flow path 119 for discharging at least a part of the cells in the culture tank 111. For example, by discharging at least a part 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 can be kept constant. Thereby, an increase in the cell density can be suppressed, and a shortage of oxygen and culture solution components or an increase in the impurity concentration in the culture solution can be prevented. The step of discharging at least a part of the cells in the culture tank 111 is referred to as cell bleeding. It should be noted that sampling may also be performed using the flow path 119 for analyzing the culture solution in the culture tank 111, but sampling is not for the purpose of adjusting the cell density, so it is different from cell bleeding.

[0803] The culture tank 111 may be provided with at least any 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.

[0804] [Method for determining the structure of the porous membrane]

[0805] The characteristic quantity of pores, the aperture ratio, the fiber diameter, and the anisotropy of the structure on the liquid contact surface structure of the porous membrane can be determined by the following method.

[0806] [Method for obtaining an image of the liquid contact surface of the porous membrane]

[0807] When the porous membrane is a hollow fiber membrane, the central part of the hollow fiber membrane is cut parallel to the fiber length direction using a razor to expose the inner surface, and it is fixed to the observation specimen stage of a scanning electron microscope (SEM) with carbon paste. For the prepared specimen, osmium coating is performed using an osmium coater (HPC-30W, manufactured by Vacuum Device Co., Ltd.) under the conditions of setting the voltage application adjustment knob to 4.5 and the discharge time to 3 seconds as the observation specimen. The electron beam is irradiated to the observation specimen according to the following conditions, and the field of view angle is adjusted so that the up-down direction of the image is parallel to the fiber length direction of the hollow fiber membrane. In the field of view consisting only of the skeletal resin and pores, the contrast is adjusted by the automatic function. The magnification that can illustrate the inner surface pore size distribution, with more than 5 and less than 60 maximum pores in the up-down direction of the image and more than 7 and less than 60 maximum pores in the horizontal direction of the image, is used as the shooting magnification. For example, the inner surface shooting magnification of the hollow fiber membrane used in the first example of the porous membrane described later is 150 times, the inner surface shooting magnification of the hollow fiber membrane used in the second example of the porous membrane is 5k times, and the inner surface shooting magnification of the hollow fiber membrane used in the third example of the porous membrane is 3k times. A reflected electron image composed of the inner surface resin skeleton and inner surface pores, excluding the specimen stage, carbon paste, and razor cutting surface, is obtained in a state where there is no structural deformation caused by charge-up and no abnormal contrast. It should be noted that when the porous membrane is a membrane other than the hollow fiber membrane, the liquid contact surface is photographed in the same way.

[0808] (SEM device conditions)

[0809] SEM: Scanning electron microscope SU7000 manufactured by Hitachi High-Technologies Corporation

[0810] Probe current: Normal

[0811] Accelerating voltage: 1 kV

[0812] Working distance: 6 mm

[0813] Detector: MD detector (reflected electron image)

[0814] Image size: 960 vertical × 1280 horizontal pixels

[0815] For a kind of hollow fiber membrane, three batches of hollow fiber membranes are used respectively. For each batch, SEM images of more than 3 non-overlapping fields of view (a total of more than 9) are obtained.

[0816] [Calculation method of the opening ratio C 0 ’ of the liquid contact surface of the porous membrane]

[0817] Remove the labels (text and scale bar parts) of the electron microscope image by trimming. For this image, after filtering using median filtering with a 5×5 square kernel, two non-zero thresholds are determined by the Multi-Otsu method. The larger value within these thresholds is used as the threshold, and pixels below the threshold are set to black, while pixels outside are set to white for image binarization. Note that the brightness of white is 255 and the brightness of black is 0. For the binarized image, a single closing process is performed using a 2×2 square kernel to remove noise. For the obtained first analysis object image, the total number of pixels in the entire image is set as A 0 , the number of black pixels is set as B 0 , and the porosity C of one SEM image is calculated by the following formula (1) 0 (%).

[0818] C 0 = B 0 × 100 / A 0 (1)

[0819] Regarding a hollow fiber membrane, the porosity C is calculated using more than 3 SEM images (a total of 9) in each of 3 batches for each field of view 0 . The arithmetic mean of these porosities C 0 is taken as the porosity C 0 ’ of the inner surface of the hollow fiber membrane

[0820] Conventionally, it has been known that using a membrane with a high porosity in filtration can suppress deterioration of water permeability due to clogging (International Publication No. 2001 / 053213). However, the inventors of the present invention have conducted in-depth research and as a result, confirmed that a method with a low porosity of the porous membrane used for tangential flow filtration in perfusion culture exhibits excellent filtration performance. Although not bound by theory, it is considered that in tangential flow filtration in perfusion culture, when the porosity is low, substances that cause membrane clogging are less likely to enter the interior of the membrane from the primary side, and substances that cause membrane clogging remain on the primary side. Therefore, a method with a small porosity of the liquid contact surface has a tendency to be less likely to cause membrane pore clogging due to accumulation of removed substances on the membrane surface

[0821] [Calculation method of fiber diameter F’ of liquid contact surface of porous membrane]

[0822] For the first analysis object image, use the filters.local_thickness function of the porespy library (2.0.2) in 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.). Set the first independent variable as the first analysis object image, set the second independent variable as mode='dt', and perform the analysis. The filter.local_thickness function is a function that analyzes white pixels in the first analysis object image. Therefore, when analyzing the first analysis object image, calculate the fiber diameter (unit: pixel), which is the diameter of the resin skeleton. Multiply the diameter (unit: pixel) by the pixel resolution (unit: m / pixel) to obtain the diameter (unit: m). The total number D of white pixels can be used. 0 and the sum E of all the obtained diameters 0 The fiber diameter F in one SEM image is represented by the following formula (2).

[0823] F = E 0 / D 0 (2)

[0824] By assigning a diameter to each pixel, F becomes the weighted average of the fiber diameters in the SEM image. For a kind of hollow fiber membrane, use more than 3 batches of 3 fields of view each (9 in total) of SEM images to calculate the fiber diameter F. Take the numerical average of the fiber diameters F of all these SEM images as the fiber diameter F' of the inner surface of the hollow fiber membrane.

[0825] Here, in the local thickness method used in the filters.local_thickness function, as Figure 2 shown, the diameter is obtained by sequentially filling circles from large to small into the region enclosed by the contour. Therefore, as Figure 3 shown, it is not necessary for the region enclosed by the contour 500 of the circle 501 to be circular. In addition, as Figure 4 shown, the region enclosed by the contour 502 is not necessarily a closed region completely enclosed by line segments. For the fibers and membrane pores on the surfaces of porous membranes with various shapes, the effective diameters used in filtration can be calculated. The following method using the filters.local_thickness function is the same.

[0826] [Calculation method for the pore diameter I' of the liquid contact surface of the porous membrane]

[0827] Perform black-and-white conversion on the first analysis object image to obtain the second analysis object image, which makes the white pixels in the first analysis object image become black and the black pixels become white. Use the filters.local_thickness function of the porespy (2.0.2) library in python (3.7.10) described in Reference 1, set the first independent variable as the second analysis object image, and set the second independent variable as mode='dt' for analysis. The filter.local_thickness function is a function that analyzes the white pixels in the second analysis object image. Therefore, when analyzing the second analysis object image, the pore size (unit: pixel) can be calculated. Multiply the diameter (unit: pixel) by the pixel resolution (unit: m / pixel) to obtain the diameter (unit: m). The total number G of white pixels and the sum H of all the obtained diameters can be used to represent the pore size I in one SEM image by the following formula (3). By assigning a diameter to each pixel, the pore size I becomes the weighted average of the pore sizes in the SEM image.

[0828] I = H / G (3)

[0829] For a hollow fiber membrane, use more than 3 batches of 3 fields of view each (9 in total) of SEM images to calculate the pore size I. Take the numerical average of the pore sizes I of all these SEM images as the pore size I' of the inner surface of the hollow fiber membrane.

[0830] [Calculation method for coefficient of variation V of pore size on liquid contact surface of porous membrane]

[0831] Set the standard deviation of the pore size I of all the above SEM images as S, and the coefficient of variation V of the pore size I is given by the following formula (4).

[0832] V = S / I' (4)

[0833] A large coefficient of variation of the pore size means a large deviation of the pore size. Generally, if the deviation of the pore size is large, in a cell culture solution with various sizes and states of inclusions, the inclusions are likely to be attracted to the surface of the porous membrane and become the accumulation points of the inclusions on the surface of the porous membrane. Therefore, the method with a small coefficient of variation of the pore size on the liquid contact surface has a tendency to be less likely to cause membrane pore blockage due to the accumulation of removed substances on the membrane surface.

[0834] [Calculation of pore size / fiber diameter J' on liquid contact surface of porous membrane]

[0835] Use the pore size I and fiber diameter F in each SEM image to give the pore size / fiber diameter ratio J by the following formula (5).

[0836] J = I / F (5)

[0837] For a hollow fiber membrane, SEM images of three batches each with three fields of view (a total of nine or more) are used to calculate the pore diameter / fiber diameter ratio J. The arithmetic mean of the pore diameter / fiber diameter ratio J in all of these SEM images is taken as the pore diameter / fiber diameter J' of the inner surface of the hollow fiber membrane. The ratio of the pore diameter to the fiber diameter...

Claims

1. A method for manufacturing a cell product, which includes the step of filtering a culture solution of cells with a porous membrane to obtain the product of the cells, The porous membrane has a liquid contact surface, and the liquid contact surface has at least any one selected from the group consisting of an opening ratio 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 The liquid contact surface has at least any one selected from the group consisting of a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and Set the shear stress generated by the flow of the culture solution on the liquid contact surface to 4.0 N / m 2 or less.

2. The method for manufacturing a cell product according to claim 1, wherein, The porous membrane has at least any one selected from the group consisting of an average pore diameter of 1 μm or more on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 3 or more.

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

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

5. The method for manufacturing a cell product according to claim 4, wherein, The hollow fiber membrane has an inclined structure in which the average pore diameter becomes smaller from the primary side to the secondary side in the membrane thickness direction.

6. The method for manufacturing a cell product according to claim 4, wherein, The exclusion pore diameter of the pores of the hollow fiber membrane is 0.05 μm or more and 20 μm or less.

7. The method for manufacturing a cell product according to claim 4, wherein, The hollow fiber membrane contains a synthetic polymer membrane.

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

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

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

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

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

13. The method for manufacturing a cell product according to claim 10, wherein, The hollow fiber membrane contains a synthetic polymer membrane.

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

15. The method for manufacturing a cell product according to claim 1 further includes the following steps: measuring the shear stress based on the viscosity of the culture solution, and controlling the flow velocity in the direction parallel to the membrane surface of the culture solution filtered through the porous membrane in such a manner that the measured shear stress becomes 4.0 N / m 2 or less.

16. The method for manufacturing a cell product according to claim 1, wherein, The culture solution not filtered by the hollow fiber membrane is returned to the culture tank of the cells.

17. The method for manufacturing a cell product according to claim 1, wherein, The product is an antibody.

18. The method for manufacturing a cell product according to claim 1, Among them, the cells were subjected to perfusion culture.

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

20. A method for producing a cell product, which comprises a step of obtaining the product of the cells by filtering the culture solution of the cells with a porous membrane, the porous membrane has a liquid contact surface, and the liquid contact surface has at least any one selected from the group consisting of an opening ratio 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 the liquid contact surface has at least any one selected from the group consisting of a structural anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more, and Set the shear stress generated by the flow of the culture medium on the liquid contact surface to 4.0 N / m 2 or more.

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 homogeneous structure that is homogeneous from the primary side to the secondary side in the membrane thickness direction.

23. The method for producing a cell product according to claim 21, wherein, the exclusion pore diameter of the pores of 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 comprises 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 method for manufacturing a cell product according to claim 20 further includes the following steps: measuring the shear stress based on the viscosity of the culture solution, and controlling the flow velocity in the direction parallel to the membrane surface of the culture solution filtered through the porous membrane in such a manner that the measured shear stress becomes 4.0 N / m 2 or more.

27. The method for producing a cell product according to claim 20, wherein, the culture solution not filtered by the hollow fiber membrane is returned to the culture tank of the cells.

28. The method for producing a cell product according to claim 20, wherein, the product is an antibody.

29. The method for producing a cell product according to claim 20, wherein, the cells were subjected to perfusion culture.

30. A method for suppressing a decrease in the membrane permeability of a cell product, which comprises a step of obtaining the product of the cells by filtering the culture solution of the cells with a porous membrane, the porous membrane has a liquid contact surface, and the liquid contact surface has at least any one selected from the group consisting of an opening ratio 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 the liquid contact surface has at least any one selected from the group consisting of a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less, and Set the shear stress generated by the flow of the culture medium on the liquid contact surface to 4.0 N / m 2 Thereafter, the reduction in the membrane permeability of the cell product is suppressed thereby.

31. The method for suppressing a decrease in the membrane permeability of a cell product according to claim 30, wherein, the porous membrane has at least any one selected from the group consisting of an average pore diameter of 1 μm or more on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 3 or more.

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

33. The method for inhibiting the reduction in the membrane permeability of cell products according to claim 31, wherein, the porous membrane is a hollow fiber membrane.

34. The method for inhibiting the reduction in the membrane permeability of cell products according to claim 33, wherein, the hollow fiber membrane has an inclined structure in the membrane thickness direction with a gradually decreasing average pore size from the primary side to the secondary side.

35. The method for inhibiting the reduction in the membrane permeability of cell products according to claim 33, wherein, the rejection pore size of the pores of the hollow fiber membrane is 0.05 μm or more and 20 μm or less.

36. The method for inhibiting the reduction in the membrane permeability of cell products according to claim 33, wherein, the hollow fiber membrane comprises a synthetic polymer membrane.

37. The method for inhibiting the reduction in the membrane permeability of cell products according to claim 36, wherein, the synthetic polymer is polysulfone.

38. The method for inhibiting the reduction in the membrane permeability of cell products according to claim 33, wherein, the hollow fiber membrane has a coarse layer and a dense layer.

39. The method for inhibiting the reduction in the membrane permeability of cell products according to claim 32, wherein, the porous membrane is a hollow fiber membrane.

40. The method for inhibiting the reduction in the membrane permeability of cell products according to claim 39, wherein, the hollow fiber membrane has a substantially homogeneous structure in the membrane thickness direction from the primary side to the secondary side.

41. The method for inhibiting the reduction in the membrane permeability of cell products according to claim 39, wherein, the rejection pore size of the pores of the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

42. The method for inhibiting the reduction in the membrane permeability of cell products according to claim 39, wherein, the hollow fiber membrane comprises a synthetic polymer membrane.

43. The method for inhibiting the reduction in the membrane permeability of cell products according to claim 42, wherein, the synthetic polymer is polyvinylidene fluoride.

44. The method for suppressing the reduction in the membrane permeability of a cell product according to claim 30 further comprises the following steps: measuring the shear stress based on the viscosity of the culture solution, and controlling the flow velocity of the culture solution filtered through the porous membrane in the direction parallel to the membrane surface in such a manner that the measured shear stress becomes 4.0 N / m 2 or less.

45. The method for inhibiting the reduction in the membrane permeability of cell products according to claim 30, wherein, the culture medium not filtered by the hollow fiber membrane is returned to the culture tank of the cells.

46. The method for inhibiting the reduction in the membrane permeability of cell products according to claim 30, wherein, the product is an antibody.

47. The method for inhibiting the reduction in the membrane permeability of cell products according to claim 30, wherein, the cells are subjected to perfusion culture.

48. The method for inhibiting the reduction in the membrane permeability of cell products according to claim 32, wherein, The density of the cells contained in the culture solution is 8×10 7 cells / mL or more.

49. A method for inhibiting the reduction in the membrane permeability of cell products, which comprises the step of filtering the culture medium of cells with a porous membrane to obtain the products of the cells, the porous membrane has a liquid contact surface, and the liquid contact surface has at least any 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 diameter of 1.3 or less, and the liquid contact surface has at least any one selected from the group consisting of a structure anisotropy degree of 0.97 or less and a major axis / minor axis of the pores of 1.8 or more, and Set the shear stress generated by the flow of the culture medium on the liquid contact surface to 4.0 N / m 2 or more, thereby suppressing a decrease in the membrane permeability of the cell product.

50. The method for suppressing the reduction in the membrane permeability of a cell product according to claim 49, wherein, the porous membrane is a hollow fiber membrane.

51. The method for suppressing the reduction in the membrane permeability of a cell product according to claim 50, wherein, the hollow fiber membrane has a substantially homogeneous structure that is homogeneous from the primary side to the secondary side in the membrane thickness direction.

52. The method for suppressing the reduction in the membrane permeability of a cell product according to claim 50, wherein, the cut-off pore diameter of the pores of the hollow fiber membrane is 0.05 μm or more and 10 μm or less.

53. The method for suppressing the reduction in the membrane permeability of a cell product according to claim 50, wherein, the hollow fiber membrane comprises a synthetic polymer membrane.

54. The method for suppressing the reduction in the membrane permeability of a cell product according to claim 53, wherein, the synthetic polymer is polyvinylidene fluoride.

55. The method for suppressing the reduction of the membrane permeability of the cell product according to claim 49 further comprises the following steps: measuring the shear stress based on the viscosity of the culture solution, and controlling the flow rate of the culture solution filtered through the porous membrane in the direction parallel to the membrane surface in such a manner that the measured shear stress becomes 4.0 N / m 2 or more.

56. The method for suppressing the reduction in the membrane permeability of a cell product according to claim 49, wherein, the culture solution that has not been filtered by the hollow fiber membrane is returned to the culture tank of the cells.

57. The method for suppressing the reduction in the membrane permeability of a cell product according to claim 49, wherein, the product is an antibody.

58. The method for suppressing the reduction in the membrane permeability of a cell product according to claim 49, wherein, the cells are subjected to perfusion culture.

59. A cell product manufacturing system, comprising: a culture tank for culturing cells, a porous membrane for filtering the culture solution of the cells to obtain the product of the cells, a pump for transporting the culture solution from the culture tank to the porous membrane, and The shear stress generated by the flow of the culture solution on the liquid contact surface of the porous membrane is made to be 4.0 N / m 2 The control unit of the pump is controlled in the following manner the liquid contact surface has at least any one selected from the group consisting of an opening ratio 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 the liquid contact surface has at least any one selected from the group consisting of a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of the pores of 1.8 or less.

60. The cell product manufacturing system according to claim 59, wherein, the porous membrane has at least any one selected from the group consisting of an average pore diameter of 1 μm or more on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 3 or more.

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

62. The cell product manufacturing system according to claim 60, wherein, the porous membrane is a hollow fiber membrane.

63. The cell product manufacturing system according to claim 62, wherein, the hollow fiber membrane has an inclined structure in which the average pore diameter becomes smaller from the primary side to the secondary side in the membrane thickness direction.

64. The cell product manufacturing system according to claim 62, wherein, the cut-off pore diameter of the pores of the hollow fiber membrane is 0.05 μm or more and 20 μm or less.

65. The manufacturing system of the cell product according to claim 62, wherein, the hollow fiber membrane comprises a synthetic polymer membrane.

66. The manufacturing system of the cell product according to claim 65, wherein, the synthetic polymer is polysulfone.

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

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

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

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

71. The manufacturing system of the cell product according to claim 68, wherein, the hollow fiber membrane comprises a synthetic polymer membrane.

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

73. The manufacturing system of the cell product according to claim 59, wherein, The control unit measures the shear stress based on the viscosity of the culture solution, and controls the flow velocity in the direction parallel to the membrane surface of the culture solution filtered through the porous membrane in such a manner that the measured shear stress becomes 4.0 N / m 2 or less.

74. The manufacturing system of the cell product according to claim 59, wherein, the control unit receives an input of the viscosity data of the culture solution.

75. The manufacturing system of the cell product according to claim 59, wherein, it further comprises a flow path for returning the culture solution that has not been filtered by the hollow fiber membrane to the culture tank.

76. The manufacturing system of the cell product according to claim 59, wherein, the product is an antibody.

77. The manufacturing system of the cell product according to claim 59, wherein, the cells are subjected to perfusion culture.

78. The manufacturing system of the cell product according to claim 61, wherein, The density of the cells contained in the culture solution is 8×10 7 cells / mL or more.

79. A manufacturing system of a cell product, comprising: a culture tank for culturing cells, a porous membrane for filtering the culture solution of the cells to obtain the product of the cells, a pump for transporting the culture solution from the culture tank to the porous membrane, and Control the control unit of the pump in such a way that the shear stress generated by the flow of the culture medium on the liquid contact surface of the porous membrane becomes 4.0 N / m 2 or more. the liquid contact surface has at least any one selected from the group consisting of an aperture ratio 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 the liquid contact surface has at least any one selected from the group consisting of a structure anisotropy degree of 0.97 or less and a major axis / minor axis of pores of 1.8 or more.

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

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

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

83. The manufacturing system of the cell product according to claim 80, wherein, The hollow fiber membrane includes a synthetic polymer membrane.

84. The cell product manufacturing system according to claim 83, wherein, the synthetic polymer is polyvinylidene fluoride.

85. The cell product manufacturing system according to claim 79, wherein, The control unit measures the shear stress based on the viscosity of the culture solution, and controls the flow velocity of the culture solution filtered through the porous membrane in the direction parallel to the membrane surface in such a manner that the measured shear stress becomes 4.0 N / m 2 or more.

86. The cell product manufacturing system according to claim 79, wherein, the control unit receives an input of the viscosity data of the culture solution.

87. The cell product manufacturing system according to claim 79, wherein, it further includes a flow path for returning the culture solution that has not been filtered by the hollow fiber membrane to the culture tank.

88. The cell product manufacturing system according to claim 79, wherein, the product is an antibody.

89. The cell product manufacturing system according to claim 79, wherein, the cells are subjected to perfusion culture.

90. A method for manufacturing a cell product, which includes a step of filtering a culture solution of cells with a porous membrane to obtain the product of the cells, the porous membrane has a liquid contact surface, and the liquid contact surface has at least any one selected from the group consisting of an opening ratio 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 the liquid contact surface has at least any one selected from the group consisting of a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane has at least any one selected from the group consisting of an average pore diameter of 10 μm or less of the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less, and The density of the cells contained in the culture solution to be filtered is 8×10 7 cells / mL or more.

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

92. The method for manufacturing a cell product according to claim 90, wherein, the culture solution that has not been filtered by the hollow fiber membrane is returned to the culture tank of the cells.

93. The method for manufacturing a cell product according to claim 90, wherein, the product is an antibody.

94. The method for manufacturing a cell product according to claim 90, wherein, the cells are subjected to perfusion culture.

95. A method for suppressing a decrease in the membrane permeability of a cell product, which includes a step of filtering a culture solution of cells with a porous membrane to obtain the product of the cells, the porous membrane has a liquid contact surface, and the liquid contact surface has at least any one selected from the group consisting of an opening ratio 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 the liquid contact surface has at least any one selected from the group consisting of a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane has at least any one selected from the group consisting of an average pore diameter of 10 μm or less of the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less, and Set the density of cells contained in the culture solution to be filtered to 8×10 7 cells / mL or more, thereby suppressing a decrease in the membrane permeability of cell products.

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

97. The method for suppressing the reduction of the membrane permeability of a cell product according to claim 95, wherein, the culture solution not filtered by the hollow fiber membrane is returned to the culture tank of the cells.

98. The method for suppressing the reduction of the membrane permeability of a cell product according to claim 95, wherein, the product is an antibody.

99. The method for suppressing the reduction of the membrane permeability of a cell product according to claim 95, wherein, the cells are subjected to perfusion culture.

100. A cell product manufacturing system, comprising: a culture tank for culturing cells, a porous membrane for filtering the culture solution of the cells to obtain the product of the cells, and a pump for transporting the culture solution from the culture tank to the porous membrane, the liquid contact surface of the porous membrane has at least any one selected from the group consisting of an opening ratio 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 the liquid contact surface has at least any one selected from the group consisting of a structural anisotropy degree of 0.97 or more and 1.03 or less and a major axis / minor axis of pores of 1.8 or less, and the porous membrane has at least any one selected from the group consisting of an average pore diameter of 10 μm or less on the liquid contact surface and a maximum value / minimum value of the average pore diameter in the membrane thickness direction of 1 or more and 10 or less, and The density of the cells contained in the culture solution to be filtered is 8 × 10 7 cells / mL or more.

101. The cell product manufacturing system according to claim 100, wherein, the porous membrane is a hollow fiber membrane.

102. The cell product manufacturing system according to claim 100, wherein, the culture solution not filtered by the hollow fiber membrane is returned to the culture tank of the cells.

103. The cell product manufacturing system according to claim 100, wherein, the product is an antibody.

104. The cell product manufacturing system according to claim 100, wherein, the cells are subjected to perfusion culture.

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