WO2024106441A1 - 細胞産生物の製造方法、細胞産生物の精製方法、細胞産生物の膜透過率の低下を抑制する方法、細胞産生物の製造システム、及び細胞産生物の精製システム - Google Patents

細胞産生物の製造方法、細胞産生物の精製方法、細胞産生物の膜透過率の低下を抑制する方法、細胞産生物の製造システム、及び細胞産生物の精製システム Download PDF

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WO2024106441A1
WO2024106441A1 PCT/JP2023/040994 JP2023040994W WO2024106441A1 WO 2024106441 A1 WO2024106441 A1 WO 2024106441A1 JP 2023040994 W JP2023040994 W JP 2023040994W WO 2024106441 A1 WO2024106441 A1 WO 2024106441A1
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liquid
contacting surface
cell product
membrane
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PCT/JP2023/040994
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English (en)
French (fr)
Japanese (ja)
Inventor
峻 松田
雄也 杉山
祐太 齊藤
ほのか 根本
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Asahi Kasei Medical Co Ltd
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Asahi Kasei Medical Co Ltd
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Priority to KR1020257014205A priority Critical patent/KR20250078531A/ko
Priority to KR1020257014171A priority patent/KR20250078526A/ko
Priority to EP23891588.8A priority patent/EP4621062A1/en
Priority to EP25203403.8A priority patent/EP4647486A3/en
Priority to KR1020257014206A priority patent/KR20250078532A/ko
Priority to CN202380077340.1A priority patent/CN120153085A/zh
Priority to US19/129,866 priority patent/US20260062664A1/en
Priority to JP2024558901A priority patent/JPWO2024106441A1/ja
Application filed by Asahi Kasei Medical Co Ltd filed Critical Asahi Kasei Medical Co Ltd
Priority to EP25203439.2A priority patent/EP4644526A3/en
Publication of WO2024106441A1 publication Critical patent/WO2024106441A1/ja
Anticipated expiration legal-status Critical
Priority to US19/233,489 priority patent/US20250361289A1/en
Priority to US19/233,505 priority patent/US20250361290A1/en
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D69/00—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor
    • B01D69/02—Semi-permeable membranes for separation processes or apparatus characterised by their form, structure or properties; Manufacturing processes specially adapted therefor characterised by their properties
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/04—Cell isolation or sorting
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IG], e.g. monoclonal or polyclonal antibodies
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D61/00—Processes of separation using semi-permeable membranes, e.g. dialysis, osmosis or ultrafiltration; Apparatus, accessories or auxiliary operations specially adapted therefor
    • B01D61/14—Ultrafiltration; Microfiltration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D63/00—Apparatus in general for separation processes using semi-permeable membranes
    • B01D63/02—Hollow fibre modules
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K1/00—General methods for the preparation of peptides, i.e. processes for the organic chemical preparation of peptides or proteins of any length
    • C07K1/14—Extraction; Separation; Purification
    • C07K1/34—Extraction; Separation; Purification by filtration, ultrafiltration or reverse osmosis
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M25/00—Means for supporting, enclosing or fixing the microorganisms, e.g. immunocoatings
    • C12M25/02—Membranes; Filters
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M27/00—Means for mixing, agitating or circulating fluids in the vessel
    • C12M27/02—Stirrer or mobile mixing elements
    • C12M27/06—Stirrer or mobile mixing elements with horizontal or inclined stirrer shaft or axis
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/04—Filters; Permeable or porous membranes or plates, e.g. dialysis
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/10—Perfusion
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/14—Pressurized fluid
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/16—Hollow fibers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M29/00—Means for introduction, extraction or recirculation of materials, e.g. pumps
    • C12M29/18—External loop; Means for reintroduction of fermented biomass or liquid percolate
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M33/00—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus
    • C12M33/14—Means for introduction, transport, positioning, extraction, harvesting, peeling or sampling of biological material in or from the apparatus with filters, sieves or membranes
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/12—Means for regulation, monitoring, measurement or control, e.g. flow regulation of temperature
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/40—Means for regulation, monitoring, measurement or control, e.g. flow regulation of pressure
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
    • C12M41/46—Means for regulation, monitoring, measurement or control, e.g. flow regulation of cellular or enzymatic activity or functionality, e.g. cell viability
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/10—Separation or concentration of fermentation products
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M47/00—Means for after-treatment of the produced biomass or of the fermentation or metabolic products, e.g. storage of biomass
    • C12M47/12—Purification
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2311/00—Details relating to membrane separation process operations and control
    • B01D2311/16—Flow or flux control
    • B01D2311/165—Cross-flow velocity control
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2315/00—Details relating to the membrane module operation
    • B01D2315/10—Cross-flow filtration
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D2325/00—Details relating to properties of membranes
    • B01D2325/02—Details relating to pores or porosity of the membranes
    • B01D2325/022—Asymmetric membranes
    • B01D2325/023—Dense layer within the membrane
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/06—Organic material
    • B01D71/30—Polyalkenyl halides
    • B01D71/32—Polyalkenyl halides containing fluorine atoms
    • B01D71/34—Polyvinylidene fluoride
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01D—SEPARATION
    • B01D71/00—Semi-permeable membranes for separation processes or apparatus characterised by the material; Manufacturing processes specially adapted therefor
    • B01D71/06—Organic material
    • B01D71/66—Polymers having sulfur in the main chain, with or without nitrogen, oxygen or carbon only
    • B01D71/68—Polysulfones; Polyethersulfones

Definitions

  • the present invention relates to a filtration technology, a method for producing a cell product, a method for purifying a cell product, a method for suppressing a decrease in membrane permeability of a cell product, a system for producing a cell product, and a system for purifying a cell product.
  • adhesion culture cells are attached to the inner surface of the culture tank.
  • suspension culture cells are suspended in the culture solution.
  • suspension culture is the mainstream due to the ease of scale-up and control on a large scale.
  • What is important in continuous culture is to efficiently separate the cells in the culture solution from the old culture solution and cell products over a long period of time, to remove the old culture solution and cell products outside the culture tank, and to continue to maintain the cell growth environment in the culture tank under optimal conditions for a long period of time.
  • the objective of the present invention is to provide a method for producing cell products, a method for purifying cell products, a method for suppressing the decrease in membrane permeability of cell products, a system for producing cell products, and a system for purifying cell products, all of which are capable of suppressing the decrease in the permeability of cell products through the porous membrane.
  • a method for producing a cell product comprising: filtering a cell culture solution with a porous membrane to obtain a cell product, wherein the porous membrane has a liquid-contacting surface having at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, and the shear stress due to the flow of the culture solution on the liquid-contacting surface is 4.0 N/ m2 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a pore size/fiber size coefficient of variation of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter/fiber diameter ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and the liquid-contacting surface may have a structural anisotropy degree of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the porous membrane has at least one selected from the group consisting of an average pore size of 1 ⁇ m or more at the liquid-contacting surface, and a maximum/minimum value of the average pore size in three or more thickness directions.
  • the porous membrane may have an average pore size of 1 ⁇ m or more at the liquid-contacting surface.
  • the porous membrane may have three or more maximum/minimum average pore sizes in the membrane thickness direction.
  • the porous membrane may have an average pore size of 1 ⁇ m or more at the liquid-contacting surface, and maximum/minimum average pore sizes in three or more thickness directions.
  • the porous membrane has at least one selected from the group consisting of an average pore size of 10 ⁇ m or less at the liquid-contacting surface, and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface.
  • the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface, and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • [7] A method for producing a cell product according to any one of [4] to [6], wherein the hollow fiber membrane is made of a synthetic polymer membrane.
  • [17] A method for producing a cell product described in any one of [ 1] to [16], further comprising 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 a direction parallel to the membrane surface so that the measured shear stress is 4.0 N/m2 or less.
  • a method for purifying a cell product comprising filtering a cell culture solution with a porous membrane to purify a cell product, wherein the porous membrane has a liquid-contacting surface having at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, and the shear stress due to the flow of the culture solution on the liquid-contacting surface is 4.0 N/ m2 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore diameter/fiber diameter ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and the liquid-contacting surface may have a structural anisotropy degree of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the porous membrane has at least one selected from the group consisting of an average pore size of 1 ⁇ m or more at the liquid-contacting surface, and maximum/minimum average pore sizes in three or more thickness directions.
  • the porous membrane may have an average pore size of 1 ⁇ m or more at the liquid-contacting surface.
  • the porous membrane may have three or more maximum/minimum average pore sizes in the membrane thickness direction.
  • the porous membrane may have an average pore size of 1 ⁇ m or more at the liquid-contacting surface, and maximum/minimum average pore sizes in three or more directions along the membrane thickness.
  • the porous membrane has at least one selected from the group consisting of an average pore size of 10 ⁇ m or less at the liquid-contacting surface, and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface.
  • the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface, and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • [34] A method for purifying a cell product according to any one of [31] to [33], wherein the hollow fiber membrane is made of a synthetic polymer membrane.
  • [38] A method for purifying a cell product according to any one of [21] to [37], in which the culture medium not filtered through the hollow fiber membrane is returned to the cell culture tank.
  • [40] A method for purifying a cell product according to any one of [21] to [39], wherein the cells are perfusion cultured.
  • a method for producing a cell product comprising filtering a cell culture solution with a porous membrane to obtain a cell product, wherein the porous membrane has a liquid-contacting surface having at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 or less, and a pore major axis/minor axis ratio of 1.8 or more, and the shear stress due to the flow of the culture solution on the liquid-contacting surface is 4.0 N/ m2 or more.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a pore size/fiber size coefficient of variation of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore diameter/fiber diameter ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter/fiber diameter ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis/minor axis ratio of 1.8 or more.
  • a method for purifying a cell product comprising filtering a cell culture solution with a porous membrane to purify a cell product, wherein the porous membrane has a liquid-contacting surface having at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 or less, and a pore major axis/minor axis ratio of 1.8 or more, and the shear stress due to the flow of the culture solution on the liquid-contacting surface is 4.0 N/ m2 or more.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore diameter/fiber diameter ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter/fiber diameter ratio of 1.3 or less, and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis/minor axis ratio of 1.8 or more.
  • [54] A method for purifying a cell product according to [52] or [53], wherein the blocking pore size of the hollow fiber membrane is 0.05 ⁇ m or more and 10 ⁇ m or less.
  • [55] A method for purifying a cell product according to any one of [52] to [54], wherein the hollow fiber membrane is made of a synthetic polymer membrane.
  • [58] A method for purifying a cell product according to any one of [51] to [57], in which the culture medium not filtered through the hollow fiber membrane is returned to the cell culture tank.
  • [60] A method for purifying a cell product according to any one of [51] to [59], wherein the cells are perfusion cultured.
  • a method for suppressing a decrease in membrane permeability of the cell product comprising 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 opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, the liquid-contacting surface having at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, and controlling the shear stress due to the flow of the culture solution on the liquid-contacting surface to 4.0 N/ m2 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter/fiber diameter ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, and the liquid-contacting surface may have a structural anisotropy degree of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the porous membrane may have an average pore size of 1 ⁇ m or more at the liquid-contacting surface.
  • the porous membrane may have three or more maximum/minimum values of average pore size in the membrane thickness direction.
  • the porous membrane may have an average pore size of 1 ⁇ m or more at the liquid-contacting surface, and maximum/minimum average pore sizes in three or more membrane thickness directions.
  • the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface.
  • the porous membrane may have a maximum/minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface, and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • [66] A method for suppressing a decrease in membrane permeability of a cell product according to [64] or [65], wherein the blocking pore size of the hollow fiber membrane is 0.05 ⁇ m or more and 20 ⁇ m or less.
  • [67] A method for suppressing a decrease in membrane permeability of a cell product according to any one of [64] to [66], wherein the hollow fiber membrane is made of a synthetic polymer membrane.
  • a method for suppressing a decrease in membrane permeability of a cell product according to any one of [64] to [68], wherein the hollow fiber membrane has a coarse layer and a dense layer.
  • [72] A method for suppressing a decrease in membrane permeability of a cell product according to [71], in which the hollow fiber membrane has a substantially uniform structure in the membrane thickness direction from the primary side to the secondary side.
  • [73] A method for suppressing a decrease in membrane permeability of a cell product according to [71] or [72], wherein the blocking pore size of the hollow fiber membrane is 0.05 ⁇ m or more and 10 ⁇ m or less.
  • [74] A method for suppressing a decrease in membrane permeability of a cell product according to any one of [71] to [73], wherein the hollow fiber membrane is made of a synthetic polymer membrane.
  • [75] A method for suppressing a decrease in membrane permeability of a cell product according to [74], wherein the synthetic polymer is polyvinylidene fluoride.
  • [78] A method for suppressing a decrease in membrane permeability of a cell product according to any one of [61] to [77], in which the culture medium not filtered through the hollow fiber membrane is returned to the cell culture tank.
  • [80] A method for suppressing a decrease in membrane permeability of a cell product according to any one of [61] to [79], wherein the cells are perfusion cultured.
  • a method for suppressing a decrease in membrane permeability of the cell product comprising 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 opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, the liquid-contacting surface having at least one selected from the group consisting of a structural anisotropy of 0.97 or less, and a pore major axis/minor axis ratio of 1.8 or more, and the shear stress due to the flow of the culture solution on the liquid-contacting surface being 4.0 N/ m2 or more.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and a structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a pore size/fiber size coefficient of variation of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore diameter/fiber diameter ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter/fiber diameter ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis/minor axis ratio of 1.8 or more.
  • [84] A method for suppressing a decrease in membrane permeability of a cell product according to [82] or [83], wherein the blocking pore size of the hollow fiber membrane is 0.05 ⁇ m or more and 10 ⁇ m or less.
  • [88] A method for suppressing a decrease in membrane permeability of a cell product according to any one of [81] to [87], in which the culture medium not filtered through the hollow fiber membrane is returned to the cell culture tank.
  • [90] A method for suppressing a decrease in membrane permeability of a cell product according to any one of [81] to [89], wherein the cells are perfusion cultured.
  • a system for producing a cell product comprising: a culture tank for culturing cells; a porous membrane for filtering a cell culture solution to obtain a cell product; a pump for sending the culture solution from the culture tank to the porous membrane; and a control unit for controlling the pump so that the shear stress due to the flow of the culture solution on the liquid-contacting surface of the porous membrane is 4.0 N/ m2 or less, wherein the liquid-contacting surface has at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber diameter of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a pore size/fiber size coefficient of variation of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and the liquid-contacting surface may have a structural anisotropy degree of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the porous membrane has at least one selected from the group consisting of an average pore size of 1 ⁇ m or more at the liquid-contacting surface, and maximum/minimum average pore size in three or more membrane thickness directions.
  • the porous membrane may have an average pore size of 1 ⁇ m or more at the liquid-contacting surface.
  • the porous membrane may have three or more maximum/minimum values of average pore size in the membrane thickness direction.
  • the porous membrane may have an average pore size of 1 ⁇ m or more at the liquid-contacting surface, and maximum/minimum average pore sizes in three or more membrane thickness directions.
  • the porous membrane has at least one selected from the group consisting of an average pore size of 10 ⁇ m or less at the liquid contact surface, and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface.
  • the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface, and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • [96] A system for producing a cell product according to [94] or [95], in which the blocking pore size of the hollow fiber membrane is 0.05 ⁇ m or more and 20 ⁇ m or less.
  • [102] A system for producing a cell product according to [101], in which the hollow fiber membrane has a substantially uniform structure in the membrane thickness direction from the primary side to the secondary side.
  • [103] A system for producing a cell product according to [101] or [102], in which the blocking pore size of the hollow fiber membrane is 0.05 ⁇ m or more and 10 ⁇ m or less.
  • [104] A system for producing a cell product according to any one of [101] to [103], wherein the hollow fiber membrane is made of a synthetic polymer membrane.
  • a cell product manufacturing system according to any one of [91] to [107], wherein the control unit receives input data on the viscosity of the culture medium.
  • [111] A system for producing a cell product according to any one of [91] to [110], in which the culture tank cultures cells by perfusion.
  • a system for producing a cell product comprising: a culture tank for culturing cells; a porous membrane for filtering a cell culture solution to obtain a cell product; a pump for sending the culture solution from the culture tank to the porous membrane; and a control unit for controlling the pump so that a shear stress due to the flow of the culture solution on the liquid-contacting surface of the porous membrane is 4.0 N/ m2 or more, wherein the liquid-contacting surface has at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 or less, and a pore major axis/minor axis of 1.8 or more.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, and the pore major axis/minor axis ratio of the liquid-contacting surface may be 1.8 or more.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis/minor axis of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis/minor axis ratio of 1.8 or more.
  • [114] A system for producing a cell product according to [113], in which the hollow fiber membrane has a substantially uniform structure in the membrane thickness direction from the primary side to the secondary side.
  • [116] A system for producing a cell product according to any one of [113] to [115], wherein the hollow fiber membrane is made of a synthetic polymer membrane.
  • control unit measures 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 a direction parallel to the membrane surface so that the measured shear stress is 4.0 N/m2 or more.
  • a cell product manufacturing system according to any one of [112] to [118], wherein the control unit receives input data on the viscosity of the culture medium.
  • [121] A system for producing a cell product according to any one of [112] to [120], wherein the product is an antibody.
  • [122] A system for producing a cell product according to any one of [112] to [121], in which the culture tank cultures cells by perfusion.
  • a system for purifying a cell product comprising: a culture tank for culturing cells; a porous membrane for filtering a cell culture solution to purify a cell product; a pump for sending the culture solution from the culture tank to the porous membrane; and a control unit for controlling the pump so that a shear stress due to the flow of the culture solution on the liquid-contacting surface of the porous membrane is 4.0 N/ m2 or less, wherein the liquid-contacting surface has at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber diameter of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less.
  • the liquid-contacting surface may have an open area ratio of 57.5% or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore size coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and the liquid-contacting surface may have a structural anisotropy degree of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy degree of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less.
  • the porous membrane has at least one selected from the group consisting of an average pore size of 1 ⁇ m or more at the liquid-contacting surface, and maximum/minimum values of the average pore size in three or more membrane thickness directions.
  • the porous membrane may have an average pore size of 1 ⁇ m or more at the liquid-contacting surface.
  • the porous membrane may have three or more maximum/minimum average pore sizes in the membrane thickness direction.
  • the porous membrane may have an average pore size of 1 ⁇ m or more at the liquid-contacting surface, and maximum/minimum average pore size values in three or more membrane thickness directions.
  • the porous membrane has at least one selected from the group consisting of an average pore size of 10 ⁇ m or less at the liquid-contacting surface, and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface.
  • the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface, and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • a purification system for cell products according to any one of [126] to [128], wherein the hollow fiber membrane is made of a synthetic polymer membrane.
  • a purification system for cell products according to any one of [126] to [130], wherein the hollow fiber membrane has a coarse layer and a dense layer.
  • a purification system for cell products according to any one of [133] to [135], wherein the hollow fiber membrane is made of a synthetic polymer membrane.
  • [140] A purification system for a cell product according to any one of [123] to [139], wherein the control unit receives input data on the viscosity of the culture medium.
  • a purification system for a cell product according to any one of [123] to [141], wherein the product is an antibody.
  • a purification system for a cell product according to any one of [123] to [142], in which the culture tank cultures cells by perfusion.
  • a system for purifying a cell product comprising: a culture tank for culturing cells; a porous membrane for filtering a cell culture solution to purify a cell product; a pump for sending the culture solution from the culture tank to the porous membrane; and a control unit for controlling the pump so that a shear stress due to the flow of the culture solution on the liquid-contacting surface of the porous membrane is 4.0 N/ m2 or more, wherein the liquid-contacting surface has at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 or less, and a pore major axis/minor axis of 1.8 or more.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, and the liquid-contacting surface may have a degree of structural anisotropy of 0.97 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or more.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore diameter/fiber diameter ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and the liquid-contacting surface may have a structural anisotropy degree of 0.97 or less and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less and a pore major axis/minor axis of 1.8 or more.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis/minor axis ratio of 1.8 or more.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or less, and a pore major axis/minor axis ratio of 1.8 or more.
  • a purification system for cell products according to any one of [145] to [147], wherein the hollow fiber membrane is made of a synthetic polymer membrane.
  • control unit measures shear stress based on the viscosity of the culture solution and controls the flow rate of the culture solution being filtered through the porous membrane in a direction parallel to the membrane surface so that the measured shear stress is 4.0 N/ m2 or more.
  • a purification system for a cell product according to any one of [144] to [150], wherein the control unit receives input data on the viscosity of the culture medium.
  • a purification system for a cell product according to any one of [144] to [152], wherein the product is an antibody.
  • a purification system for a cell product according to any one of [144] to [153], in which the culture tank cultures cells by perfusion.
  • a method for producing a cell product comprising filtering a cell culture solution with a porous membrane to obtain a cell product, wherein the porous membrane has a liquid-contacting surface having at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, the liquid-contacting surface having at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, the porous membrane has at least one selected from the group consisting of an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10, and the density of cells contained in the culture solution to be filtered is 8 x 107 cells/mL or more.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface.
  • the liquid-contacting surface may have a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter at the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum/minimum average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the film thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the film thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a long diameter/short diameter of the pores of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore long axis/short axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore long axis/short axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore diameter in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a long axis/short axis of the pores of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore diameter in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a pore long axis/short axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have pore major axis/minor axis ratios of 1.8 or less, and the porous membrane may have maximum/minimum average pore sizes in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long diameter/short diameter of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long axis/short axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long axis/short axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore diameter in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long axis/short axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore diameter in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface and a maximum/minimum average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface and a maximum/minimum value of the average pore size in the film thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface and a maximum/minimum average pore size in the film thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface and a maximum/minimum average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore size in the film thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a long diameter/short diameter of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and the liquid-contacting surface may have a pore long axis/short axis of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 ⁇ m or less, and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore long axis/short axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less at the liquid-contacting surface, and a maximum/minimum average pore diameter in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a long axis/short axis of the pores of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 ⁇ m or less and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum average pore diameter in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a pore long axis/short axis of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 ⁇ m or less, and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less, and a maximum/minimum average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a long axis/short axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long axis/short axis of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long axis/short axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less at the liquid-contacting surface and a maximum/minimum average pore diameter in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a long axis/short axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore diameter in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • a method for purifying a cell product comprising filtering a cell culture solution with a porous membrane to purify a cell product, wherein the porous membrane has a liquid-contacting surface having at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, the liquid-contacting surface having at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, the porous membrane has at least one selected from the group consisting of an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10, and the density of cells contained in the culture solution to be filtered is 8 x 107 cells/mL or more.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy degree of 0.97 to 1.03, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore diameter/fiber diameter ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore diameter on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have a structural anisotropy degree of 0.97 to 1.03, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the film thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum/minimum average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the film thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the film thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a long axis/short axis ratio of the pores of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore diameter in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a long axis/short axis of the pores of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore diameter in the film thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long axis/short axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long axis/short axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore diameter in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore diameter in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long axis/short axis ratio of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface and a maximum/minimum value of the average pore size in the film thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a long axis/short axis ratio of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 ⁇ m or less, and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum average pore diameter in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a long axis/short axis ratio of the pores of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 ⁇ m or less and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum average pore diameter in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less, and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less, and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long axis/short axis of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 ⁇ m or less and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long axis/short axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface and a maximum/minimum value of the average pore diameter in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore diameter in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • [171] A method for purifying a cell product according to any one of [164] to [170], wherein the product is an antibody.
  • a method for suppressing a decrease in membrane permeability of cell products comprising filtering a cell culture solution with a porous membrane to obtain a cell product, the method comprising: filtering the cell culture solution with a porous membrane, the porous membrane having a liquid-contacting surface having at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, the liquid-contacting surface having at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, the porous membrane having at least one selected from the group consisting of an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10, and the density of cells contained in the culture solution to be filtered is 8 x
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have a structural anisotropy degree of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore diameter/fiber diameter ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore diameter on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a structural anisotropy degree of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have a structural anisotropy degree of 0.97 to 1.03, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a long axis/short axis ratio of the pores of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore diameter in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a long axis/short axis of the pores of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore diameter in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have pore major axis/minor axis ratios of 1.8 or less, and the porous membrane may have maximum/minimum average pore sizes in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a structural anisotropy degree of 0.97 to 1.03 and a pore long axis/short axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long axis/short axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore diameter in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long axis/short axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore diameter in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have a structural anisotropy degree of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 ⁇ m or less, and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a long axis/short axis ratio of pores of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore long axis/short axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 ⁇ m or less, and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less at the liquid-contacting surface, and a maximum/minimum value of the average pore diameter in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a long axis/short axis ratio of the pores of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 ⁇ m or less and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore diameter in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 ⁇ m or less, and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less, and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a long axis/short axis of pores of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long axis/short axis of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 ⁇ m or less and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long diameter/short diameter of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore diameter in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less, and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • [175] A method for suppressing a decrease in membrane permeability of a cell product according to [174], wherein the hollow fiber membrane has a substantially uniform structure from the primary side to the secondary side in the membrane thickness direction.
  • [176] A method for suppressing a decrease in membrane permeability of a cell product according to [174] or [175], wherein the blocking pore size of the hollow fiber membrane is 0.05 ⁇ m or more and 10 ⁇ m or less.
  • a method for suppressing a decrease in membrane permeability of a cell product according to any one of [174] to [176], wherein the hollow fiber membrane is made of a synthetic polymer membrane.
  • a method for suppressing a decrease in membrane permeability of a cell product according to any one of [174] to [178], in which the culture medium not filtered through the hollow fiber membrane is returned to the cell culture tank.
  • a method for suppressing a decrease in membrane permeability of a cell product according to any one of [173] to [179], wherein the product is an antibody.
  • [181] A method for suppressing a decrease in membrane permeability of a cell product according to any one of [173] to [180], wherein the cells are perfusion cultured.
  • a system for producing a cell product comprising: a culture tank for culturing cells; a porous membrane for filtering a cell culture solution to obtain a cell product; and a pump for transporting the culture solution from the culture tank to the porous membrane, wherein the liquid-contacting surface of the porous membrane has at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, the porous membrane has at least one selected from the group consisting of an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10, and the density of cells contained in the culture solution to be
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting 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 on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long axis/short axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have a structural anisotropy degree of 0.97 to 1.03, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum/minimum average pore diameter in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the film thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum/minimum average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the film thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, and the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the film thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a long axis/short axis of the pores of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have pore major axis/minor axis values of 1.8 or less, and the porous membrane may have maximum/minimum average pore size values in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore long axis/short axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore diameter in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a long axis/short axis of the pores of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore diameter in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a pore long axis/short axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a structural anisotropy degree of 0.97 to 1.03 and a pore long axis/short axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long axis/short axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long axis/short axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore diameter in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long axis/short axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore diameter in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long diameter/short diameter ratio of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface and a maximum/minimum average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface and a maximum/minimum value of the average pore size in the film thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface and a maximum/minimum average pore size in the film thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface and a maximum/minimum average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore size in the film thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a long axis/short axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore long axis/short axis of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 ⁇ m or less, and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore long axis/short axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum average pore diameter in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a long axis/short axis of the pores of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum average pore diameter in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a pore long axis/short axis of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less, and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a long axis/short axis of the pores of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less, and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a long axis/short axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a long axis/short axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long axis/short axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface and a maximum/minimum value of the average pore diameter in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a long axis/short axis of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore diameter in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long diameter/short diameter ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • a cell product manufacturing system according to any one of [182] to [188], further comprising a flow path for returning the culture solution not filtered by the hollow fiber membrane to the culture tank.
  • [191] A system for producing a cell product according to any one of [182] to [190], in which the culture tank cultures cells by perfusion.
  • a system for purifying a cell product comprising: a culture tank for culturing cells; a porous membrane for filtering a cell culture solution to purify a cell product; and a pump for transporting the culture solution from the culture tank to the porous membrane, wherein the liquid-contacting surface of the porous membrane has at least one selected from the group consisting of an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, and the liquid-contacting surface has at least one selected from the group consisting of a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, and the porous membrane has at least one selected from the group consisting of an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10, and the density of cells contained in the culture solution
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have a structural anisotropy degree of 0.97 to 1.03, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy degree of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy degree of 0.97 to 1.03, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter at the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore diameter/fiber diameter ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore diameter on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have a structural anisotropy degree of 0.97 to 1.03, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have a maximum/minimum average pore size in the film thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, the liquid-contacting surface may have a long axis/short axis of the pores of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have pore major axis/minor axis values of 1.8 or less, and the porous membrane may have maximum/minimum average pore size values in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore diameter in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a major axis/minor axis of the pores of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore diameter in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long axis/short axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore diameter in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have a maximum/minimum average pore diameter in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less at the liquid-contacting surface and a maximum/minimum value of the average pore size in the film thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 or more and 1.03 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore size in the film thickness direction of 1 or more and 10 or less.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have a long axis/short axis ratio of the pores of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore size at the liquid-contacting surface of 10 ⁇ m or less, and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum average pore diameter in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a major axis/minor axis of the pores of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum average pore diameter in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less, and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size on the liquid-contacting surface of 10 ⁇ m or less, and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface and a maximum/minimum average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long axis/short axis of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface and a maximum/minimum value of the average pore size in the membrane thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore long axis/short axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface and a maximum/minimum value of the average pore diameter in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less and a pore size with a coefficient of variation of 0.5 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03 and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening ratio of 57.5% or less, and a pore diameter/fiber diameter of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore diameter of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore diameter in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • the liquid-contacting surface may have an opening rate of 57.5% or less, a pore size with a coefficient of variation of 0.5 or less, and a pore size/fiber size ratio of 1.3 or less, the liquid-contacting surface may have a structural anisotropy of 0.97 to 1.03, and a pore major axis/minor axis ratio of 1.8 or less, and the porous membrane may have an average pore size of 10 ⁇ m or less on the liquid-contacting surface, and a maximum/minimum value of the average pore size in the film thickness direction of 1 to 10.
  • a purification system for a cell product according to any one of [192] to [199], wherein the product is an antibody.
  • a purification system for a cell product according to any one of [192] to [200], in which the culture tank cultures cells by perfusion.
  • the present invention can provide a method for producing a cell product, a method for purifying a cell product, a method for suppressing a decrease in membrane permeability of a cell product, a system for producing a cell product, and a system for purifying a cell product, which can suppress a decrease in the permeability of the cell product in a porous membrane.
  • FIG. 1 is a schematic diagram illustrating a cell product manufacturing system according to an embodiment.
  • FIG. 4 is a diagram illustrating an example of image processing according to the embodiment.
  • FIG. 13 is a diagram showing an example of image processing when calculating the structural anisotropy Z′ of the porous membrane surface according to the embodiment.
  • FIG. 2 is a diagram showing a schematic diagram of the flow velocity distribution and the shear stress distribution of a fluid flowing through a hollow portion when the porous membrane according to the embodiment is a hollow fiber membrane.
  • 1 is a graph showing the relationship between the shear stress at the liquid-contacting surface of a hollow fiber membrane according to an example and the antibody permeability at a filtration volume of 300 L/ m2 .
  • 1 is a graph showing the relationship between the shear stress at the liquid-contacting surface of a hollow fiber membrane according to an embodiment and the transmembrane pressure at a filtration rate of 300 L/ m2 .
  • 1 is a graph showing the relationship between shear stress at the liquid-contacting surface of a hollow fiber membrane according to an example and antibody permeability at a filtration volume of 300 L/ m2 .
  • 1 is a graph showing the relationship between the shear stress at the liquid-contacting surface of a hollow fiber membrane according to an embodiment and the transmembrane pressure difference at a filtration rate of 300 L/ m2 .
  • 1 is a graph showing the relationship between the shear stress at the liquid-contacting surface of a hollow fiber membrane according to an example and the antibody permeability at a filtration volume of 300 L/ m2 .
  • 1 is a graph showing the relationship between the shear stress at the liquid-contacting surface of a hollow fiber membrane according to an embodiment and the transmembrane pressure difference at a filtration rate of 300 L/ m2 .
  • present embodiment The following provides a detailed explanation of the form for carrying out the present invention (hereinafter referred to as the "present embodiment"). Note that the present embodiment is intended to facilitate understanding of the present invention, and is not intended to limit the interpretation of the present invention. The present invention is not limited to the present embodiment, and can be carried out in various modifications within the scope of the gist of the present invention.
  • the method for producing a cell product includes filtering a cell culture solution with a porous membrane 112 to obtain a cell product.
  • the cell culture solution is sent from a culture tank 111 to the porous membrane 112.
  • the culture tank 111 may have a vent or a filter with a pore size of 0.2 ⁇ m or less to prevent external bacteria from entering the inside of the culture tank 111.
  • the culture tank 111 may be provided with an agitator 212 for agitating the culture solution in the culture tank 111. Cells are cultured in suspension in the culture solution in the culture tank 111.
  • the cells cultured in the culture tank 111 are not particularly limited.
  • the cells may be derived from animals, including humans, or from microorganisms.
  • the cells may be eukaryotic or prokaryotic. Examples of animals include mammals, reptiles, birds, amphibians, fish, and insects.
  • the cells may be genetically modified cells. Examples of cells include CHO (Chinese Hamster Ovary) cells, HEK cells, BHK-21 cells, Sp2/0 cells, SP2/0-Ag14 cells, NS0 cells, Vero cells, PER. C6 cells, yeast, Bacillus subtilis, and Escherichia coli.
  • the cells may, for example, produce and release a medicamentous product into the culture medium.
  • medicamentous products include peptides, proteins, and viruses (including virus-like particles).
  • proteins include antibodies, hormones, cytokines, growth factors, enzymes, and plasma proteins.
  • the protein may be a recombinant protein.
  • the antibody may be a monoclonal antibody or a polyclonal antibody.
  • the antibody may be a human antibody or an antibody protein derived from a non-human mammal such as a cow or a mouse.
  • the antibody may be a chimeric antibody protein with human IgG, or a humanized antibody.
  • a chimeric antibody with human IgG is an antibody in which the variable region is derived from a non-human organism such as a mouse, but the other constant regions are replaced with immunoglobulins derived from humans.
  • a humanized antibody is an antibody in which the complementarity-determining region (CDR) of the variable region is derived from a non-human organism, but the other framework regions (FR) are derived from humans. Humanization further reduces immunogenicity compared to chimeric antibodies.
  • the cells in the culture fluid are removed, and the product of the cells in the culture fluid permeates the porous membrane 112 and is purified.
  • the surface that comes into contact with the culture fluid to be filtered is called the liquid-contacting surface.
  • the shape of the porous membrane 112 is not particularly limited. Examples of porous membranes include hollow fiber membranes, flat membranes, and tubular membranes. In the following, an example in which the porous membrane 112 is a hollow fiber membrane will be described. In the hollow fiber membrane, the liquid-contacting surface to which the cell culture fluid is supplied is called the primary side of the hollow fiber membrane.
  • the surface from which the permeated fluid that has permeated the hollow fiber membrane flows out is called the secondary side of the hollow fiber membrane.
  • the inner peripheral surface of the hollow fiber membrane is the primary side
  • the outer peripheral surface of the hollow fiber membrane is the secondary side.
  • the cell culture fluid to be filtered is supplied to the outer peripheral surface
  • the outer peripheral surface of the hollow fiber membrane is the primary side
  • the inner peripheral surface of the hollow fiber membrane is the secondary side.
  • the filtration method in the porous membrane 112 may be a tangential flow filtration (TFF) method.
  • the tangential flow filtration method is a filtration method in which the culture solution is made to flow in a direction parallel to the primary surface of the hollow fiber membrane on the primary surface of the hollow fiber membrane.
  • the tangential flow filtration method includes an alternating tangential flow filtration (ATF) method.
  • ATF alternating tangential flow filtration
  • ATF tangential flow filtration
  • the alternating tangential flow filtration (ATF) method refers to a filtration method in which the culture solution is made to flow back and forth on the primary surface of the hollow fiber membrane.
  • a flow path 113 for sending the culture liquid in the culture tank 111 to the porous membrane 112, and a flow path 114 for returning the culture liquid that has passed through the hollow part of the porous membrane 112 without passing through the pores of the porous membrane 112 and has passed through the porous membrane 112 without being filtered by the porous membrane 112 to the culture tank 111.
  • the culture liquid flowing through the flow path 113 may contain cells and products of the cells.
  • the culture liquid flowing through the flow path 114 without being filtered by the porous membrane 112 may contain cells and products of the cells.
  • a flow path 115 is connected to the porous membrane 112 for collecting the culture liquid that has passed through the pores of the porous membrane 112 and been filtered.
  • the culture liquid flowing through the flow path 115 and filtered by the porous membrane 112 may contain products of the cells.
  • the culture liquid filtered by the porous membrane 112 is collected, for example, in a container 201.
  • the container 201 may be connected to the flow path 115 in a sterile manner.
  • the flow path 115 through which the culture solution filtered through the porous membrane 112 flows may be directly connected to a column used for the next purification step, for example.
  • the flow path 113 is provided with, for example, a pump 123 for sending the culture solution in the culture tank 111 to the porous membrane 112.
  • pumps include, but are not limited to, a diaphragm pump, a tube pump, a centrifugal pump, and a rotary pump.
  • the flow path 113 may be provided with a pressure gauge 133 for measuring the pressure of the culture solution supplied to the porous membrane 112.
  • the flow path 113 may be provided with a flow meter for measuring at least one of the flow rate and flow rate of the culture solution flowing 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.
  • the flow path 114 may be provided with a pump for sending the culture solution that does not pass through the pores of the porous membrane 112 but passes through the hollow part and is not filtered by the porous membrane 112 to the culture tank 111.
  • the pump may be provided in both the flow path 113 and the flow path 114, or 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 one of the flow rate 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 when sampling.
  • the flow path 115 is provided with, for example, a pump 125 for sending the culture solution filtered by the porous membrane 112 through the pores of the porous membrane 112.
  • the flow path 115 may be provided with a pressure gauge 135 for measuring the pressure of the culture solution filtered by the porous membrane 112.
  • the flow path 115 may be provided with a flow meter for measuring at least one of the flow rate and flow rate of the culture solution flowing through the flow path 115.
  • the flow path 115 may be provided with a sampling section for sampling the culture solution flowing through the flow path 115. The sampling section is closed except when sampling.
  • the culture tank 111 and the porous membrane 112 form at least a part of the path through which the culture medium circulates.
  • the flow paths 113 and 114 form at least a part of the path through which the culture medium circulates.
  • the culture tank 111 may be connected to a flow path 116 for supplying the culture fluid to the culture tank 111.
  • the flow path 116 is connected to, for example, a culture fluid tank 216 that contains the culture fluid.
  • the flow path 116 is provided with, for example, a pump 126 for sending the culture fluid to the culture tank 111.
  • the pumps 125 and 126 are controlled so that the amount of culture fluid that is filtered by the porous membrane 112 and does not return to the culture tank 111 is the same as the amount of culture fluid supplied to the culture tank 111.
  • This control may be performed by observing the liquid level using a liquid level sensor (level sensor) installed in the culture tank 111 so that the liquid level is constant, or by measuring the weight of the entire culture tank 111 containing the culture fluid so that the weight is constant.
  • level sensor level sensor
  • 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 is connected to, for example, a container 217 that contains air containing carbon dioxide.
  • the culture tank 111 may be connected to a flow path 118 for supplying oxygen to the culture tank 111.
  • the flow path 118 is connected to, for example, a container 218 that contains oxygen.
  • the culture tank 111 may be connected to a flow path 119 for discharging at least a portion of the cells in the culture tank 111.
  • a flow path 119 for discharging at least a portion of the cells in the culture tank 111.
  • the cell density in the culture solution in the culture tank 111 is kept constant. This prevents the cell density from increasing, resulting in a shortage of oxygen and culture solution components in the culture solution, and an increase in the concentration of impurities.
  • Discharging at least a portion of the cells in the culture tank 111 is called bleeding.
  • the flow path 119 may be used to perform sampling for analyzing the culture solution in the culture tank 111, but sampling is distinguished from bleeding because it is not intended to adjust the cell density.
  • the culture tank 111 may be provided with at least one of a thermometer for measuring the temperature of the culture solution in the culture tank 111, a DO meter for measuring DO (dissolved oxygen), and a pH meter for measuring pH.
  • a thermometer for measuring the temperature of the culture solution in the culture tank 111
  • DO meter for measuring DO (dissolved oxygen)
  • pH meter for measuring pH.
  • the pore features, aperture ratio, fiber diameter, and structural anisotropy in the liquid-contacting surface structure of the porous membrane can be determined by the following method.
  • the porous membrane is a hollow fiber membrane
  • the hollow fiber membrane is cut in the center parallel to the fiber length direction with a razor to expose the inner surface, and fixed with carbon paste on the observation sample stage of a scanning electron microscope (SEM).
  • SEM scanning electron microscope
  • the prepared sample is osmium coated using an osmium coater (HPC-30W, manufactured by Vacuum Device Co., Ltd.) under the conditions of an applied voltage adjustment knob setting of 4.5 and a discharge time of 3 seconds to prepare an observation sample.
  • the observation sample is irradiated with an electron beam under the following conditions, and the viewing angle is adjusted so that the vertical direction of the image is parallel to the fiber length direction of the hollow fiber membrane.
  • the contrast is adjusted by the auto function in a field of view consisting of only the skeleton resin and pores.
  • the magnification that can explain the inner surface pore size distribution is set to a magnification that includes 5 to 60 largest pores in the vertical direction of the image and 7 to 60 largest pores in the horizontal direction of the image.
  • the magnification of the inner surface of the hollow fiber membrane used in the first example of the porous membrane described later is 150 times
  • the magnification of the inner surface of the hollow fiber membrane used in the second example of the porous membrane is 5k times
  • the magnification of the inner surface of the hollow fiber membrane used in the third example of the porous membrane is 3k times.
  • a backscattered electron image is obtained that is free of structural distortion and abnormal contrast due to charge-up, and is composed of the inner surface resin skeleton and inner surface pores, and does not include the sample stage, carbon paste, or razor cut surface. Note that even if the porous membrane is a membrane other than a hollow fiber membrane, the liquid-contacting surface may be photographed in the same manner.
  • SEM images For each type of hollow fiber membrane, three lots of hollow fiber membranes are used, and SEM images (a total of nine or more) are obtained from three or more fields of view with no overlap for each lot.
  • the total number of pixels in the entire image is A0
  • the number of black pixels is B0
  • the aperture ratio C0 (%) of one SEM image is calculated from the following formula (1).
  • C 0 B 0 ⁇ 100 / A 0 (1)
  • the aperture ratio C0 is calculated using SEM images of at least three fields of view (total of nine images) for each of three lots.
  • the number average value of these aperture ratios C0 is defined as the aperture ratio C0 ' of the inner surface of the hollow fiber membrane.
  • the fiber diameter (unit: pixel) which is the diameter of the resin skeleton, is calculated.
  • the diameter (unit: pixel) is multiplied by the pixel resolution (unit: m/pixel) to obtain the diameter (unit: m).
  • the fiber diameter F in one SEM image can be expressed by the following formula (2).
  • F is the weighted average of the fiber diameters in the SEM image.
  • fiber diameter F is calculated using at least three SEM images from three fields of view (total of nine images) for three lots. The number average of fiber diameters F of all these SEM images is taken as fiber diameter F' on the inner surface of the hollow fiber membrane.
  • the diameter is found by filling in the circles that fit into the area surrounded by the contour, starting from the largest. Therefore, as shown in FIG. 3, the area surrounded by the contour 500 into which the circle 501 can be placed does not have to be a circle. Also, as shown in FIG. 4, the area surrounded by the contour 502 does not have to be a closed area completely surrounded by line segments. It is possible to calculate the effective diameter used in filtration for fibers and membrane pores on the surface of porous membranes of various shapes. The same applies to the method using the filters.local_thickness function described below.
  • the first analysis target image is inverted to black and white, and the pixels that were white in the first analysis target image are turned to black, and the pixels that were black in the first analysis target image are turned to white to obtain a second analysis target image.
  • the diameter (unit: pixel) is multiplied by the pixel resolution (unit: m/pixel) to obtain the diameter (unit: m).
  • pore size I is calculated using SEM images of at least three fields of view (total of nine images) for each of three lots. The number average value of pore size I of all these SEM images is taken as the pore size I' of the inner surface of the hollow fiber membrane.
  • a large coefficient of variation in pore size means that there is a large variation in pore size. If there is a large variation in pore size, in a cell culture fluid containing impurities of various sizes and states, it is thought that impurities are more likely to get caught on the porous membrane surface and become a foothold for the accumulation of impurities on the porous membrane surface. Therefore, the smaller the coefficient of variation in pore size on the liquid-contacting surface, the less likely the membrane pores will become clogged due to the accumulation of removed matter on the membrane surface.
  • the pore size/fiber diameter ratio J is calculated using SEM images of at least three fields of view (total of nine sheets) for each of three lots of one type of hollow fiber membrane.
  • the number average value of the pore size/fiber diameter ratio J in all these SEM images is taken as the pore size/fiber diameter J' on the inner surface of the hollow fiber membrane.
  • the ratio of the pore size to the fiber diameter on the liquid-contacting surface of the porous membrane is the value obtained by standardizing the effective pore size for filtration using the fiber diameter.
  • M (long axis/short axis) is calculated for all contours contained in one SEM image, and the number average value is taken as M'.
  • M' is calculated using at least three SEM images from three fields of view for each of three lots (a total of nine images).
  • the number average value of M' in all these SEM images is taken as the average value M'' of the long axis/short axis of the pores present on the inner surface of the hollow fiber membrane.
  • the ratio of the long axis to the short axis of the pores on the liquid-contacting surface of the porous membrane (long axis/short axis) is an index of the anisotropy of the pores on the liquid-contacting surface.
  • an analysis object image OI of 512 x 512 pixels with one end at the upper left vertex, an analysis object image P I of the same size as OI with one end at the lower left vertex, an analysis object image Q I of the same size as OI with one end at the upper right vertex, and an analysis object image R I of the same size as OI with one end at the lower right vertex are extracted.
  • a masking process is performed on the analysis object image OI by making the outside of a circle with a diameter of 512 pixels and the same center as OI black, and a third analysis object image for FFT analysis is obtained.
  • a two-dimensional fast Fourier transform is performed using the fft.fft2 function of the Numpy (1.20.3) library of python (3.7.10) to obtain a matrix T S.
  • the first argument of the fft.fft2 function is the third analysis object image, and the others use default settings.
  • the matrix T S is rearranged using the fft.fftshift function of Numpy (1.20.3) so that the low-frequency components are at the center to obtain a matrix T.
  • the first argument of the fft.fftshift function is the matrix T S , and the other parameters are set to default.
  • the power spectrum U is obtained by the following formula (7).
  • U 20 ⁇ log (T) (7)
  • the obtained power spectrum U is converted to polar coordinates using the warpPolar function of the OpenCV (4.5.2) library of python (3.7.10), to obtain a 360 x 360 matrix T V with the center of the power spectrum as the origin.
  • the horizontal direction of the image shown in FIG. 6 is set to 0° in polar coordinates, and polar coordinate conversion is performed in the ⁇ direction.
  • a matrix T W is obtained that represents the intensity average for each row of the matrix T V.
  • the matrix T W is a one-column matrix, and corresponds to the intensity average for each angle.
  • the intensity average is also a number average value.
  • the element average of the matrix T W is obtained by adding up all the elements of the matrix T W and dividing by the number of elements.
  • the matrix T W is divided by the element average to obtain the matrix T Y.
  • the structural anisotropy Z is calculated using SEM images of at least three fields of view (total of nine images) for each of three lots.
  • the number average of the structural anisotropy Z in all these SEM images is taken as the structural anisotropy Z' of the liquid-contacting surface of the hollow fiber membrane.
  • the structural anisotropy Z' of the porous membrane surface is 1, this indicates that the pores are uniformly oriented in the vertical and horizontal directions of the image, and that the anisotropy of the membrane structure is small.
  • the structural anisotropy Z' is greater than 1, this indicates that the membrane structure is oriented in the horizontal direction of the image.
  • the structural anisotropy Z' is less than 1, this indicates that the membrane structure is oriented in the vertical direction of the image.
  • a cross section in the thickness direction is prepared under the following cross section preparation conditions using an ion milling device E-3500 (Hitachi High-Tech Corporation).
  • the cross section is a smooth cross section in which an Ar ion beam penetrates from the outer surface to the inner surface of the hollow fiber membrane, the resin skeleton is not deformed by heat, and no sputtered sample pieces are attached. Note that even when the porous membrane is a membrane other than a hollow fiber membrane, a cross section in the thickness direction may be prepared in the same manner.
  • the cross-sectional imaging magnification of the first and second examples of the porous membrane described below is 5k times
  • the cross-sectional imaging magnification of the hollow fiber membrane used in the third example of the porous membrane is 3k times.
  • the outer surface is aligned with the right side of the SEM image, and a first backscattered electron image is obtained in which the hollow fiber membrane thickness direction and the SEM image lateral direction are parallel.
  • this backscattered electron image is an image focused on a smooth cross section, and is an image without structural distortion or abnormal contrast due to charge-up.
  • the cross section in the membrane thickness direction may be photographed in the same manner.
  • the field of view of the first backscattered electron image is shifted parallel to the film thickness direction toward the inner surface to obtain a second backscattered electron image.
  • the fields of view are slightly overlapped so that the hole structure in the second backscattered electron image and the hole structure in the first backscattered electron image are smoothly connected.
  • the process of acquiring backscattered electron images by shifting the field of view in the film thickness direction and slightly overlapping it with the previous field of view continues, and imaging is terminated when the inner surface is included in the backscattered electron image.
  • the labels (letters and scale bar parts) of the obtained backscattered electron images are trimmed off, and all the images are combined so that the pore structure is smoothly connected, to obtain a single cross-sectional SEM image.
  • the cross-sectional images are rectangular, if there is any vertical misalignment in the SEM images when they are combined, this is removed by trimming after combination.
  • the cross-section of the hollow fiber membrane is essentially circular, the aim is to obtain a high-resolution cross-section in an area that can be adequately approximated as a rectangle.
  • the cross-sectional SEM image is trimmed so that the left end is the inner surface and the right end is the outer surface to obtain a first cross-sectional SEM image.
  • the first cross-sectional SEM image has the same pixel resolution as the first backscattered electron image. If the resin skeleton present in the depth direction within the hole is observed with a brightness brighter than the cross-sectional resin, it may be hand-painted with a dark color so that the resin skeleton in the depth direction is also recognized as part of the hole in the binarization process.
  • the cross-sectional pore size analysis is performed by the following method.
  • a first region with a width of 100 pixels including the left edge is extracted.
  • the height of all extracted regions is assumed to be equal to that of the first cross-sectional SEM image.
  • the maximum diameter, the variation coefficient of the pore size, the average pore size, and the aperture ratio of the multiple pores included in the first region are calculated.
  • two non-zero thresholds are determined by the multi-Otsu method. The larger of these thresholds is used as the threshold, and the image is binarized by making pixels below the threshold white and other pixels black.
  • the brightness of white is 255 and the brightness of black is 0.
  • the binarized image is closed once using a 2 ⁇ 2 square kernel to remove noise.
  • the obtained analysis target image is filtered using the filters.
  • the local_thickness function is a function that performs analysis on white pixels in the image to be analyzed
  • the pore size (unit: pixel) is calculated.
  • the pore size (unit: pixel) is multiplied by the pixel resolution (unit: m/pixel) to obtain the pore size (unit: m).
  • the pore size is given for all pixels, and the maximum pore size among them is set as the maximum pore size I max (1) of the first region.
  • the coefficient of variation of the pore size in the pore size distribution in the image to be analyzed is defined as the coefficient of variation V1 of the first region.
  • V1 coefficient of variation of the first region.
  • I1 E1 / D1 (12)
  • the aperture ratio C 1 (%) is given by the following formula (13) using the total number of pixels A 1 in the first region.
  • C1 D1 ⁇ 100 / A1 (13)
  • the center of the first region is the center of the first region, which is 100 pixels in width in the direction perpendicular to the left edge.
  • the width W1 of the first region is narrowed according to the following formula (14) until the pore size variation coefficient V1 falls within the predetermined range, and then the maximum pore size Imax(1) , the variation coefficient V1 , the average pore size I1 , and the aperture ratio C1 are calculated again.
  • the center of the width W1 of the first region is the center of the first region.
  • the width W1 of the first region is expanded according to formula (15) until the pore size variation coefficient V1 falls within the predetermined range, and then the maximum pore size Imax(1) , the variation coefficient V1 , the average pore size I1 , and the aperture ratio C1 are calculated again.
  • the center of the width W1 of the first region is regarded as the center of the first region.
  • the finally determined average pore diameter I1 and aperture ratio C1 are recorded in association with the center coordinates of the first region.
  • the center of the n+2th region is set to be 100 pixels away from the center of the n+1th region in the direction perpendicular to the left edge of the first cross-sectional SEM image, where n is an integer with an initial value of 0.
  • the coefficient of variation of the maximum diameter and pore diameter of multiple contours included in the n+2th region is calculated.
  • two non-zero thresholds are determined by the multi-Otsu method. The larger of these thresholds is used as the threshold, and the image is binarized with pixels below the threshold as white and other pixels as black. However, the brightness of white is 255 and the brightness of black is 0.
  • the binarized image is closed once using a 2x2 square kernel to remove noise.
  • the aperture ratio C n+2 (%) is given by the following formula (18) using the total number of white pixels D n+2 and the total number of pixels A n+2 in the (n+2)th region.
  • C n +2 D n +2 ⁇ 100 / A n +2 (18)
  • the coefficient of variation V n+2 of the hole diameter in the n+2th region is within a predetermined range of more than 0.3 and less than 0.5, the width W n+2 of the n+2th region in the direction perpendicular to the left edge is maintained.
  • the width W n+2 of the n+2th region is narrowed according to formula (19) while maintaining the center of the n+2th region until the coefficient of variation V n+2 of the diameter falls within the predetermined range, and then the maximum hole diameter I max(n+2) , the coefficient of variation V n+2, the average hole diameter I n+2 , and the opening ratio C n+2 are calculated again.
  • N n+2 indicates the number of times the region is retaken until it falls within the predetermined range.
  • W n+2 (10 - 0.1 ⁇ N n+2 ) ⁇ I max (n+2) (19)
  • the width W n+2 of the n+2th region is expanded according to formula (20) while maintaining the center of the n+2th region until the diameter variation coefficient falls within the predetermined range, and then the maximum pore diameter I max(n+2) , the variation coefficient V n+2 , the average pore diameter I n+2 , and the opening ratio C n+2 are calculated again.
  • N n+2 indicates the number of times the region is retaken until it falls within the predetermined range.
  • Wn +2 (10 + 0.1 ⁇ Nn +2 ) ⁇ Imax(n+2) (20)
  • the finally determined average pore size I n+2 and aperture ratio C n+2 are recorded in association with the center coordinates of the n+2th region.
  • n is added by 1, and the calculation of the average pore size I n+1 of the n+1th region and the aperture ratio C n+1 is repeated until the center of the n+2th region exceeds the right end side of the first cross-sectional SEM image. Then, among the recorded average pore sizes I n+1 , the corresponding aperture ratio C n+1 is excluded from 80% or more.
  • the graph in which the average pore size I n+1 is plotted against the region center coordinates is compared with the first cross-sectional SEM image, if the value is obviously unnatural, the point is deleted.
  • the maximum value of the average pore size in the film thickness direction is I max
  • the minimum value of the average pore size in the film thickness direction is I min
  • the ratio R maximum value/minimum value of the maximum value and minimum value of the average pore size from the primary side surface to the secondary side surface in the film thickness direction of the porous membrane
  • the numerical average value is the maximum/minimum value R' of the average pore size in the thickness direction of the porous membrane.
  • the maximum/minimum value R' of the average pore size in the thickness direction of the porous membrane reflects the variation in the pore size in the thickness direction of the porous membrane, and is therefore closely correlated with the mechanism of progression of membrane blockage inside the porous membrane. Therefore, without being bound by theory, it is believed that there is an appropriate combination between the structural characteristics of the liquid-contacting surface of the porous membrane and the filtration conditions to exhibit excellent filtration performance.
  • the blocking pore size is exemplified as the particle size of the particles when the particle dispersion liquid in which particles of a certain particle size are dispersed is filtered using a porous hollow fiber membrane and the permeation blocking rate of the particles is 90%. It is also called the minimum pore size.
  • polystyrene latex particles manufactured by JSR Corporation, SIZE STANDARD PARTICLES
  • a 0.5% by mass aqueous solution of sodium dodecyl sulfate manufactured by Wako Pure Chemical Industries, Ltd.
  • the latex particle dispersion liquid is filtered using a porous hollow fiber membrane, and the change in concentration of the latex particles before and after filtration is measured. This measurement is performed while changing the latex particle size, and a blocking curve of the latex particles is created. From this blocking curve, the particle size that can block 90% of the permeation is read, and this diameter is taken as the blocking pore size.
  • the inner diameter ( ⁇ m) and outer diameter ( ⁇ m) of the hollow fiber membrane can be measured by cutting the hollow fiber membrane into a thin tube and observing the slice under an optical microscope (VHX-7000, manufactured by Keyence Corporation).
  • the thickness W TH ( ⁇ m) of the hollow fiber membrane can be calculated from the inner diameter W I and the outer diameter W O using the following formula (22).
  • WTH ( WO - WI ) / 2 (22)
  • shear stress SS due to the flow of the culture solution on the liquid-contacting surface of the porous membrane is given by the product of the viscosity VC (Pa s) of the culture solution flowing through the hollow part of the hollow fiber membrane and the shear rate SV (/s), as shown in the following equation (23).
  • CS VC ⁇ SV (23)
  • the viscosity of the culture medium can be affected, for example, by the temperature of the culture medium, the composition of the culture medium, and the density of cells in the culture medium.
  • antifoaming polymers that may be included in the culture medium can affect the viscosity of the culture medium.
  • the flow of the culture solution in the hollow part of the hollow fiber membrane is a Hagen-Poiseuille flow, and as shown in FIG. 7, the distribution of the flow rate of the culture solution in the hollow part of the hollow fiber membrane is a quadratic curve with the center of the hollow part of the hollow fiber membrane as the axis.
  • the shear rate of the culture solution is the slope of the quadratic curve.
  • the shear rate SV of the culture solution is maximum SVmax at the liquid-contacting surface of the hollow fiber membrane, and is given by the following formula (24), where LV is the linear velocity of the culture solution (m/s) and W I is the inner diameter (m) of the hollow part of the hollow fiber membrane.
  • the shear stress is also maximum SSmax at the liquid-contacting surface of the hollow fiber membrane.
  • SVmax 8LV/W I (24)
  • the shear stress can be calculated from the above formula (23).
  • a density polarization layer with a high cell density is formed on the inner surface (primary surface) of the hollow fiber membrane, as shown in Figure 8.
  • cells accumulate on the inner surface (primary surface) of the hollow fiber membrane, forming a cake layer.
  • the density polarization layer and cake layer cause a decrease in the permeability of the cell products without a decrease in the flow rate of the permeating liquid through the hollow fiber membrane.
  • the inside of the hollow fiber membrane is blocked by substances contained in the culture medium, the flow rate of the permeating liquid through the hollow fiber membrane decreases and the permeability of the cell products decreases.
  • Cell products such as antibodies are very expensive, so even a slight decrease in permeability has a large impact on the cost of biopharmaceuticals.
  • the permeability P (%) of the cell product is given by the following formula (25), where Q1 is the concentration of the cell product in the culture medium before filtration through the porous membrane, and Q2 is the concentration of the cell product in the culture medium after filtration through the porous membrane.
  • P Q2 x 100/Q1 (25)
  • the transmembrane pressure difference Om in the hollow fiber membrane is given by the following formula (26), where O1i is the pressure of the culture solution supplied to the primary side of the hollow fiber membrane, O1o is the pressure of the culture solution that has passed through the primary side of the hollow fiber membrane without being filtered by the hollow fiber membrane, and O2 is the pressure of the culture solution that has been filtered by the hollow fiber membrane and discharged from the secondary side.
  • Om (O1i + O1o) / 2 - O2 (26) The greater the degree of blockage inside the hollow fiber membrane, the higher the transmembrane pressure difference.
  • the aperture ratio at the liquid-contacting surface is, for example, 57.5% or less, 55% or less, or 52.5% or less.
  • the aperture ratio is, for example, 1% or more, 5% or more, or 10% or more.
  • the aperture ratio is, for example, 1% or more and 57.5% or less, 5% or more and 57.5% or less, 10% or more and 57.5% or less, 1% or more and 55% or less, 5% or more and 55% or less, 10% or more and 55% or less, 1% or more and 52.5% or less, 5% or more and 52.5% or less, or 10% or more and 52.5% or less.
  • the smaller the aperture ratio the less likely the membrane pores are to be blocked by the accumulation of removed matter on the membrane surface.
  • the structural anisotropy of the liquid-contacting surface is, for example, 0.97 or more, 0.975 or more, 0.98 or more, 0.985 or more, or 0.99 or more.
  • the structural anisotropy of the liquid-contacting surface is, for example, 1.03 or less, 1.025 or less, 1.02 or less, 1.015 or less, or 1.01 or less.
  • the structural anisotropy of the liquid-contacting surface is, for example, 0.97 or more and 1.03 or less, 0.975 or more and 1.025 or less, 0.98 or more and 1.02 or less, 0.985 or more and 1.015 or less, or 0.99 or more and 1.01 or less.
  • the smaller the anisotropy of the liquid-contacting surface the less likely the membrane pores will be blocked by the accumulation of removed material on the membrane surface.
  • the long diameter/short diameter ratio of the pores on the liquid-contacting surface is, for example, 1 or more, or 1.05 or more.
  • the long diameter/short diameter ratio of the pores is, for example, 1.8 or less, 1.75 or less, 1.7 or less, or 1.65 or less.
  • the long diameter/short diameter ratio of the pores is, for example, 1 or more and 1.8 or less, 1 or more and 1.75 or less, 1 or more and 1.7 or less, 1 or more and 1.65 or less, or 1.05 or more and 1.65 or less.
  • the smaller the anisotropy of the pores on the liquid-contacting surface the less likely the membrane pores are to be blocked by the accumulation of removed matter on the membrane surface.
  • the pore size/fiber size at the liquid-contacting surface is, for example, 0.05 or more, 0.1 or more, 0.2 or more, 0.3 or more, 0.4 or more, or 0.5 or more.
  • the pore size/fiber size at the liquid-contacting surface is, for example, 1.3 or less, 1.25 or less, 1.2 or less, 1.15 or less, or 1.1 or less.
  • the pore size/fiber size at the liquid-contacting surface is, for example, 0.05 or more and 1.3 or less, 0.1 or more and 1.3 or less, 0.2 or more and 1.3 or less, 0.3 or more and 1.3 or less, 0.4 or more and 1.25 or less, 0.4 or more and 1.2 or less, or 0.5 or more and 1.1 or less.
  • the smaller the pore size/fiber size the less likely the membrane pores are to be clogged due to the accumulation of removed matter on the membrane surface.
  • the coefficient of variation of the pore size at the liquid-contacting surface is 0 or more, 0.01 or more, 0.03 or more, or 0.05 or more.
  • the coefficient of variation of the pore size is 0.5 or less, 0.49 or less, 0.48 or less, or 0.47 or less.
  • the coefficient of variation of the pore size is 0 or more and 0.5 or less, 0.01 or more and 0.5 or less, 0.03 or more and 0.5 or less, 0.05 or more and 0.5 or less, 0.01 or more and 0.49 or less, 0.03 or more and 0.48 or less, or 0.05 or more and 0.47 or less.
  • the smaller the variation of the pore size at the liquid-contacting surface the less likely the membrane pores are to be blocked by the accumulation of removed matter on the membrane surface.
  • the ratio of the maximum value to the minimum value (maximum value/minimum value) when the average pore diameter is calculated at equal distances from the membrane surface in the membrane thickness direction is 3 or more, 5 or more, or 10 or more.
  • the maximum value/minimum value of the average pore diameter is 1000 or less, 500 or less, or 100 or less.
  • the maximum value/minimum value of the average pore diameter is 3 or more and 1000 or less, 5 or more and 1000 or less, 10 or more and 1000 or less, 3 or more and 500 or less, 5 or more and 500 or less, 10 or more and 500 or less, 3 or more and 100 or less, 5 or more and 100 or less, or 10 or more and 100 or less.
  • the greater the maximum value/minimum value of the average pore diameter is from 1, the more the pore diameter of the porous membrane fluctuates in the membrane thickness direction.
  • the porous membrane may be a hollow fiber membrane.
  • the porous structure of the hollow fiber membrane may have a gradient structure in which the average pore size decreases from the primary side toward the secondary side in the membrane thickness direction.
  • the average pore size of the primary surface is larger than the average pore size of the secondary surface, and the pore size decreases from the primary surface toward the minimum pore size layer. Note that there may be a portion between the primary surface and the secondary surface where the pore size does not change.
  • the distribution of pore sizes is asymmetric in the membrane thickness direction.
  • a layer with a relatively large pore size near the primary surface of the hollow fiber membrane is called a coarse layer.
  • a layer with a relatively small pore size near the secondary surface of the hollow fiber membrane is called a dense layer.
  • the minimum pore size layer, in which the pore size is smallest, is included in the dense layer.
  • the average pore size of the primary surface in the hollow fiber membrane having a gradient structure is, for example, 1 ⁇ m or more, 5 ⁇ m or more, 10 ⁇ m or more, or 15 ⁇ m or more.
  • the average pore size of the primary surface is, for example, 140 ⁇ m or less, 120 ⁇ m or less, 100 ⁇ m or less, or 80 ⁇ m or less.
  • the average pore size of the primary surface is, for example, 1 ⁇ m or more and 140 ⁇ m or less, 5 ⁇ m or more and 120 ⁇ m or less, 5 ⁇ m or more and 100 ⁇ m or less, 10 ⁇ m or more and 100 ⁇ m or less, 15 ⁇ m or more and 100 ⁇ m or less, or 15 ⁇ m or more and 80 ⁇ m or less.
  • a pore size of 1 ⁇ m or more on the primary surface it is easier to obtain the effect of depth filtration that retains the removed material inside the membrane, and it is less likely that the membrane pores will be blocked due to the accumulation of the removed material on the membrane surface.
  • the strength of the hollow fiber membrane tends to be easily maintained.
  • the average pore size of the secondary surface in the hollow fiber membrane having a gradient structure is, for example, 0.1 ⁇ m or more, 0.2 ⁇ m or more, or 0.3 ⁇ m or more.
  • the average pore size is, for example, 20 ⁇ m or less, 15 ⁇ m or less, 10 ⁇ m or less, 5 ⁇ m or less, or 2 ⁇ m or less.
  • the average pore size of the secondary surface is, for example, 0.1 ⁇ m to 20 ⁇ m, 0.1 ⁇ m to 15 ⁇ m, 0.1 ⁇ m to 10 ⁇ m, 0.1 ⁇ m to 5 ⁇ m, 0.1 ⁇ m to 2 ⁇ m, 0.2 ⁇ m to 15 ⁇ m, 0.3 ⁇ m to 10 ⁇ m, 0.3 ⁇ m to 5 ⁇ m, or 0.3 ⁇ m to 2 ⁇ m.
  • the blocking pore size of the hollow fiber membrane having a gradient structure is, for example, 0.05 ⁇ m or more, 0.1 ⁇ m or more, 0.2 ⁇ m or more, or 0.3 ⁇ m or more.
  • the blocking pore size of the hollow fiber membrane having a gradient structure is, for example, 20 ⁇ m or less, 10 ⁇ m or less, 5 ⁇ m or less, 3 ⁇ m or less, 1 ⁇ m or less, 0.8 ⁇ m or less, or 0.5 ⁇ m or less.
  • the blocking pore size of the hollow fiber membrane is, for example, 0.05 ⁇ m to 20 ⁇ m, 0.1 ⁇ m to 10 ⁇ m, 0.2 ⁇ m to 5 ⁇ m, 0.3 ⁇ m to 3 ⁇ m, 0.3 ⁇ m to 1 ⁇ m, 0.3 ⁇ m to 0.8 ⁇ m, or 0.3 ⁇ m to 0.5 ⁇ m. If the blocking pore size is 0.05 ⁇ m or more, it tends to suppress the permeation resistance, suppress the pressure required for filtration, and suppress clogging of the membrane surface due to destruction and deformation of microbial particles, and a decrease in filtration efficiency. Also, if the blocking pore size is 20 ⁇ m or less, sufficient fractionation tends to be obtained.
  • the hollow fiber membrane having a gradient structure may include a minimum pore size layer near the secondary surface, where the pore size is smallest.
  • the minimum pore size in the hollow fiber membrane is approximately the same as the blocking pore size.
  • the inner diameter of the hollow portion of the hollow fiber membrane is, for example, 1000 ⁇ m or more, 1100 ⁇ m or more, 1200 ⁇ m or more, or 1300 ⁇ m or more.
  • the inner diameter of the hollow portion of the hollow fiber membrane is, for example, 3000 ⁇ m or less, 2500 ⁇ m or less, 2000 ⁇ m or less, 1900 ⁇ m or less, 1800 ⁇ m or less, 1700 ⁇ m or less, 1600 ⁇ m or less, or 1500 ⁇ m or less.
  • the inner diameter of the hollow portion of the hollow fiber membrane is, for example, 1000 ⁇ m or more and 3000 ⁇ m or less, 1000 ⁇ m or more and 2500 ⁇ m or less, 1000 ⁇ m or more and 2000 ⁇ m or less, 1100 ⁇ m or more and 1900 ⁇ m or less, or 1200 ⁇ m or more and 1800 ⁇ m or less. If the inner diameter of the hollow portion is 1000 ⁇ m or more, the entrance of the hollow portion tends not to be blocked by cells. If the inner diameter of the hollow portion is 3000 ⁇ m or less, the number of hollow fiber membranes that make up the filtration module increases, the effective membrane area per filtration module increases, and the filtration performance tends to be excellent.
  • the membrane thickness of the hollow fiber membrane is, for example, 100 ⁇ m or more, 200 ⁇ m or more, 300 ⁇ m or more, or 400 ⁇ m or more.
  • the membrane thickness of the hollow fiber membrane is, for example, 1400 ⁇ m or less, 1300 ⁇ m or less, 1200 ⁇ m or less, 1100 ⁇ m or less, 1000 ⁇ m or less, 900 ⁇ m or less, 800 ⁇ m or less, 700 ⁇ m or less, 600 ⁇ m or less, or 500 ⁇ m or less.
  • the membrane thickness of the hollow fiber membrane is, for example, 100 ⁇ m or more and 1400 ⁇ m or less, 200 ⁇ m or more and 1200 ⁇ m or less, or 300 ⁇ m or more and 1000 ⁇ m or less. If the membrane thickness is 100 ⁇ m or more, the strength of the hollow fiber membrane tends to be easily maintained. Furthermore, it tends to be easy to maintain an appropriate filtration speed. Furthermore, if the membrane thickness is 1,400 ⁇ m or less, the number of hollow fiber membranes constituting the filtration module increases, the effective membrane area per filtration module increases, and filtration performance tends to be excellent.
  • the hollow fiber membrane is, for example, made of a synthetic polymer membrane.
  • the synthetic polymer is, for example, hydrophobic.
  • An example of the synthetic polymer is polysulfone, but is not limited to this.
  • impurities such as cells and debris (cell pieces) contained in the cell culture solution have a hydrophobic surface. The impurities are captured by the hollow fiber membrane due to hydrophobic interactions. This makes it possible to purify the cell culture solution containing the cell products.
  • the hollow fiber membrane according to the embodiment can be manufactured with reference to the method described in, for example, International Publication No. 2010/035793.
  • the inventors have found that the multiple liquid-contacting surface structures of the first example of the porous membrane affect the filtration performance.
  • each of the multiple liquid-contacting surface structures alone can be sufficiently effective.
  • a synergistic effect can be achieved by combining multiple liquid-contacting surface structures. For example, once the clogging of membrane pores due to the accumulation of removed matter on the membrane surface begins to progress, it is believed to progress at an accelerated rate, using the deposits as a foothold. For this reason, it is effective to use a porous membrane having a liquid-contacting surface that has multiple structural features within an appropriate range.
  • the aperture ratio at the liquid-contacting surface of the porous membrane, the coefficient of variation of the pore size at the liquid-contacting surface, the pore size/fiber size at the liquid-contacting surface, the structural anisotropy degree at the liquid-contacting surface, and the major axis/minor axis of the pores at the liquid-contacting surface are the same as those in the first example of the porous membrane.
  • the porous membrane may be a hollow fiber membrane.
  • the porous structure of the hollow fiber membrane may have a substantially uniform structure in the membrane thickness direction from the primary side to the secondary side.
  • the substantially uniform structure means that the average pore size does not change significantly, and refers to a membrane structure in which the ratio of the maximum value to the minimum value (maximum value/minimum value) when the average pore size of the part at the same distance from the membrane surface in the membrane thickness direction is calculated is 10 or less, 5 or less, or 3 or less.
  • the maximum value/minimum value of the average pore size may be 1 or more, 1.01 or more, or 1.05 or more.
  • the maximum/minimum value of the average pore size may be 1 or more and 10 or less, 1 or more and 5 or less, 1 or more and 3 or less, 1.01 or more and 10 or less, 1.01 or more and 5 or less, 1.01 or more and 3 or less, 1.05 or more and 10 or less, 1.05 or more and 5 or less, or 1.05 or more and 3 or less.
  • the average pore size of the primary surface in a hollow fiber membrane having a homogeneous structure is, for example, 0.05 ⁇ m or more, 0.1 ⁇ m or more, or 0.15 ⁇ m or more. Also, the average pore size of the primary surface is, for example, 10 ⁇ m or less, 5 ⁇ m or less, 1 ⁇ m or less, 0.9 ⁇ m or less, 0.8 ⁇ m or less, 0.7 ⁇ m or less, 0.6 ⁇ m or less, 0.5 ⁇ m or less, or 0.4 ⁇ m or less.
  • the average pore size of the primary surface is, for example, 0.05 ⁇ m to 10 ⁇ m, 0.1 ⁇ m to 5 ⁇ m, 0.15 ⁇ m to 1 ⁇ m, 0.15 ⁇ m to 0.9 ⁇ m, 0.15 ⁇ m to 0.8 ⁇ m, 0.15 ⁇ m to 0.7 ⁇ m, 0.15 ⁇ m to 0.6 ⁇ m, 0.15 ⁇ m to 0.5 ⁇ m, or 0.15 ⁇ m to 0.4 ⁇ m.
  • a pore size of 0.05 ⁇ m or more and 10 ⁇ m or less on the primary surface it is easy to obtain the effect of screen filtration that does not allow the removed material to enter the inside of the membrane while maintaining the strength of the hollow fiber membrane.
  • the blocking pore size of the hollow fiber membrane having a homogeneous structure is, for example, 0.05 ⁇ m or more, 0.1 ⁇ m or more, or 0.15 ⁇ m or more. Also, the blocking pore size of the hollow fiber membrane having a homogeneous structure is, for example, 10 ⁇ m or less, 5 ⁇ m or less, 1 ⁇ m or less, 0.8 ⁇ m or less, 0.6 ⁇ m or less, 0.4 ⁇ m or less, 0.35 ⁇ m or less, 0.3 ⁇ m or less, or 0.25 ⁇ m or less.
  • the blocking pore size of the hollow fiber membrane is, for example, 0.05 ⁇ m to 10 ⁇ m, 0.05 ⁇ m to 5 ⁇ m, 0.05 ⁇ m to 1 ⁇ m, 0.1 ⁇ m to 0.8 ⁇ m, 0.1 ⁇ m to 0.6 ⁇ m, 0.1 ⁇ m to 0.4 ⁇ m, 0.1 ⁇ m to 0.35 ⁇ m, 0.1 ⁇ m to 0.3 ⁇ m, 0.15 ⁇ m to 0.3 ⁇ m, or 0.15 ⁇ m to 0.25 ⁇ m.
  • the blocking pore size is 0.05 ⁇ m or more, the permeation resistance is suppressed, the pressure required for filtration is suppressed, and clogging of the membrane surface due to destruction and deformation of microbial particles and a decrease in filtration efficiency tend to be suppressed. Also, if the blocking pore size is 10 ⁇ m or less, sufficient fractionation tends to be obtained.
  • the inner diameter of the hollow portion of the hollow fiber membrane is, for example, 1000 ⁇ m or more, 1100 ⁇ m or more, 1200 ⁇ m or more, or 1300 ⁇ m or more.
  • the inner diameter of the hollow portion of the hollow fiber membrane is, for example, 3000 ⁇ m or less, 2500 ⁇ m or less, 2000 ⁇ m or less, 1900 ⁇ m or less, 1800 ⁇ m or less, 1700 ⁇ m or less, 1600 ⁇ m or less, or 1500 ⁇ m or less.
  • the inner diameter of the hollow portion of the hollow fiber membrane is, for example, 1000 ⁇ m or more and 3000 ⁇ m or less, 1000 ⁇ m or more and 2500 ⁇ m or less, 1000 ⁇ m or more and 2000 ⁇ m or less, 1100 ⁇ m or more and 1900 ⁇ m or less, or 1200 ⁇ m or more and 1800 ⁇ m or less. If the inner diameter of the hollow portion is 1000 ⁇ m or more, the entrance of the hollow portion tends not to be blocked by cells. If the inner diameter of the hollow portion is 3000 ⁇ m or less, the number of hollow fiber membranes that make up the filtration module increases, the effective membrane area per filtration module increases, and the filtration performance tends to be excellent.
  • the membrane thickness of the hollow fiber membrane is, for example, 100 ⁇ m or more, 200 ⁇ m or more, 300 ⁇ m or more, or 400 ⁇ m or more.
  • the membrane thickness of the hollow fiber membrane is, for example, 1400 ⁇ m or less, 1300 ⁇ m or less, 1200 ⁇ m or less, 1100 ⁇ m or less, 1000 ⁇ m or less, 900 ⁇ m or less, 800 ⁇ m or less, 700 ⁇ m or less, 600 ⁇ m or less, or 500 ⁇ m or less.
  • the membrane thickness of the hollow fiber membrane is, for example, 100 ⁇ m or more and 1400 ⁇ m or less, 200 ⁇ m or more and 1200 ⁇ m or less, or 300 ⁇ m or more and 1000 ⁇ m or less. If the membrane thickness is 100 ⁇ m or more, the strength of the hollow fiber membrane tends to be easily maintained. Furthermore, it tends to be easy to maintain an appropriate filtration speed. Furthermore, if the membrane thickness is 1,400 ⁇ m or less, the number of hollow fiber membranes constituting the filtration module increases, the effective cross-sectional area per filtration module increases, and filtration performance tends to be excellent.
  • the hollow fiber membrane is, for example, made of a synthetic polymer membrane.
  • the synthetic polymer is, for example, hydrophobic.
  • An example of a synthetic polymer includes, but is not limited to, polyvinylidene fluoride.
  • the inventors have found that the multiple liquid-contacting surface structures of the second example of the porous membrane affect the filtration performance.
  • each of the multiple liquid-contacting surface structures alone can be sufficiently effective.
  • a synergistic effect can be achieved by combining multiple liquid-contacting surface structures. For example, once the clogging of membrane pores due to the accumulation of removed matter on the membrane surface begins to progress, it is believed to progress at an accelerated rate, using the deposits as a foothold. For this reason, it is effective to use a porous membrane having a liquid-contacting surface that has multiple structural features within an appropriate range.
  • the shear stress due to the flow of the culture solution on the liquid-contacting surface of the porous membrane 112 is set to 4.0 N/ m2 or less.
  • the shear stress may be 3.75 N/ m2 or less, 3.5 N/ m2 or less, 3.25 N/ m2 or less, or 3.0 N/ m2 or less.
  • the shear stress may be 0 N/ m2 or more, 0.01 N/ m2 or more, 0.05 N/ m2 or more, or 0.1 N/ m2 or more.
  • the shear stress is 0 N/ m2 or more and 4.0 N/ m2 or less, 0.01 N/ m2 or more and 4.0 N/ m2 or less, 0.05 N/ m2 or more and 4.0 N/ m2 or less, 0.1 N/ m2 or more and 4.0 N/ m2 or less, 0 N/ m2 or more and 3.75 N/ m2 or less, 0.01 N/ m2 or more and 3.75 N/ m2 or less, 0.05 N/ m2 or more and 3.75 N/ m2 or less, 0.1 N/ m2 or more and 3.75 N/ m2 or less, 0 N/ m2 or more and 3.5 N/ m2 or less, 0.01 N/ m2 or more and 3.5 N/ m2 or less, 0.05 N/ m2 or more and 3.5 N/ m2 or less, 0.1 N/ m2 or more and 3.5 N/ m2 or less, 0 N/ m2 or more
  • porous membranes according to the first and second examples it is possible to suppress a decrease in the permeability of the cell products in the porous membrane 112 by setting the shear stress due to the culture medium on the liquid-contacting surface of the porous membrane 112 to 4.0 N/ m2 or less.
  • the shear stress may be measured based on the viscosity of the culture solution, and the flow rate of the culture solution filtered through the porous membrane 112 in a direction parallel to the membrane surface may be controlled so that the measured shear stress is 4.0 N/m 2 or less.
  • the shear stress SS, the viscosity VC of the culture solution, and the shear rate SV are related by the above formula (3).
  • the viscosity VC of the culture solution can be obtained in advance. It may be measured by a viscometer provided in the flow path 113.
  • the shear rate SV can be calculated from the linear velocity LV, and the linear velocity LV can be obtained, for example, from the output of the pump 123. It may be measured by a flow meter provided in the flow path 113.
  • the shear stress SS of the culture solution can be measured based on the known viscosity VC of the culture solution and the obtained linear velocity LV or shear rate SV of the culture solution.
  • a control unit 301 is connected to the pump 123.
  • the control unit 301 may control the pump 123 to control the linear velocity of the culture solution flowing through the porous membrane 112, thereby controlling the flow rate of the culture solution filtered through the porous membrane 112 in a direction parallel to the membrane surface so that the shear stress is 4.0 N/ m2 or less.
  • the shear stress in the porous membrane 112 is set to 4.0 N/m 2 or less, but this does not exclude the occurrence of a period in which the shear stress in the porous membrane 112 is 4.0 N/m 2 or more. For example, due to a delay in feedback control of the pump, a period in which the shear stress in the porous membrane 112 is 4.0 N/m 2 or more may occur.
  • the porous membrane according to the first and second examples it is sufficient that the shear stress in the porous membrane 112 is 4.0 N/m 2 or less for at least 80% of the entire period in which the cells are cultured.
  • the density of cells contained in the culture solution filtered by the porous membrane 112 is not particularly limited, but may be 5 ⁇ 10 cells/mL or less.
  • the cell density may be 4.5 ⁇ 10 cells/mL or less, 4 ⁇ 10 cells/mL or less, 3.5 ⁇ 10 cells/mL or less, 3 ⁇ 10 cells/mL or less, 2.5 ⁇ 10 cells/mL or less, 2 ⁇ 10 cells/mL or less, or 1.5 ⁇ 10 cells/mL or less.
  • the density of cells contained in the culture solution filtered by the porous membrane 112 is not particularly limited, but may be 0.5 ⁇ 10 cells/mL or more.
  • the cell density may be 1 ⁇ 10 cells/mL or more, 0.5 ⁇ 10 cells/mL or more, or 1 ⁇ 10 cells/mL or more.
  • the density of cells contained in the culture solution filtered by the porous membrane 112 is not particularly limited, but may be 0.5 ⁇ 10 6 cells/mL or more and 5 ⁇ 10 7 cells/mL or less.
  • the cell density is 1 ⁇ 10 6 cells/mL to 5 ⁇ 10 7 cells/mL, 0.5 ⁇ 10 7 cells/mL to 5 ⁇ 10 7 cells/mL, 1 ⁇ 10 7 cells/mL to 5 ⁇ 10 7 cells/mL, 0.5 ⁇ 10 6 cells/mL to 4.5 ⁇ 10 7 cells/mL, 0.5 ⁇ 10 6 cells/mL to 4 ⁇ 10 7 cells/mL, 0.5 ⁇ 10 6 cells/mL to 3.5 ⁇ 10 7 cells/mL, 0.5 ⁇ 10 6 cells/mL to 3 ⁇ 10 7 cells/mL, 0.5 ⁇ 10 6 cells/mL to 2.5 ⁇ 10 7 cells/mL or less, 0.5 ⁇ 10 6 cells/mL or more and 2 ⁇ 10 7 cells/mL or less, 0.5 ⁇ 10 6 cells/mL or more and 1.5 ⁇ 10
  • the density of cells contained in the culture solution filtered by the porous membrane 112 is not particularly limited, but may be, for example, 8 x 107 cells/mL or more, 8.5 x 107 cells/mL or more, 9 x 107 cells/mL or more, 9.5 x 107 cells/mL or more, 1 x 108 cells/mL or more, 1.1 x 108 cells/mL or more, 1.2 x 108 cells/mL or more, 1.3 x 108 cells/mL or more, 1.4 x 108 cells/mL or more, 1.5 x 108 cells/mL or more, or 2 x 108 cells/mL or more.
  • the degree to which the decrease in the permeability of the cell products in the porous membrane 112 is suppressed is increased under conditions in which the density of cells contained in the culture medium filtered through the porous membrane 112 is 8 x 107 cells/mL or more.
  • the more particles contained in the liquid to be filtered the faster the change in the performance of the filtration membrane is likely to progress. This is because the more particles contained in the liquid, the more particles that become foulants for the filtration membrane.
  • a higher density of cells contained in the culture solution exhibits better filtration performance. Without being bound by theory, it is believed that this is because the porous membrane according to the second example is less likely to have membrane pores blocked by the accumulation of removed matter on the membrane surface, while the cell particles present in large amounts in the solution have the effect of preventing the intrusion of foulants that cause clogging inside the membrane into the membrane.
  • the cell density is 2 ⁇ 10 9 cells/mL or less.
  • the cell density may be 1.5 x 10 9 cells/mL or less, 1.4 x 10 9 cells/mL or less, 1.3 x 10 9 cells/mL or less, 1.2 x 10 9 cells/mL or less, 1.1 x 10 9 cells/mL or less, 1 x 10 9 cells/mL or less, 9 x 10 8 cells/mL or less, 8 x 10 8 cells/mL or less, 7 x 10 8 cells/mL or less, 6 x 10 8 cells/mL or less, 5 x 10 8 cells/mL or less, 4 x 10 8 cells/mL or less, or 3 x 10 8 cells/mL or less.
  • the density of cells contained in the culture solution filtered by the porous membrane 112 is not particularly limited, but may be 8 ⁇ 10 7 cells/mL or more and 2 ⁇ 10 9 cells/mL or less.
  • the cell densities were 8.5 ⁇ 10 7 cells/mL to 2 ⁇ 10 9 cells/mL, 9 ⁇ 10 7 cells/mL to 2 ⁇ 10 9 cells/mL, 9.5 ⁇ 10 7 cells/mL to 2 ⁇ 10 9 cells/mL, 1 ⁇ 10 8 cells/mL to 2 ⁇ 10 9 cells/mL, 1.1 ⁇ 10 8 cells/mL to 2 ⁇ 10 9 cells/mL, 1.2 ⁇ 10 8 cells/mL to 2 ⁇ 10 9 cells/mL, 1.3 ⁇ 10 8 cells/mL to 2 ⁇ 10 9 cells/mL, and 1.4 ⁇ 10 8 cells/mL to 2 ⁇ 10 9.
  • the opening ratio at the liquid-contacting surface of the porous membrane, the coefficient of variation of the pore size at the liquid-contacting surface, and the pore size/fiber size at the liquid-contacting surface are the same as those of the first example of the porous membrane.
  • the structural anisotropy of the liquid-contacting surface is 0.97 or less, 0.965 or less, 0.96 or less, or 0.955 or less.
  • the structural anisotropy of the liquid-contacting surface may be 0.3 or more, 0.5 or more, 0.7 or more, 0.8 or more, or 0.9 or more.
  • the structural anisotropy of the liquid-contacting surface may be 0.3 or more and 0.97 or less, 0.5 or more and 0.97 or less, 0.7 or more and 0.97 or less, 0.8 or more and 0.97 or less, 0.9 or more and 0.97 or less, 0.5 or more and 0.965 or less, 0.7 or more and 0.96 or less, or 0.8 or more and 0.955 or less.
  • the greater the anisotropy of the liquid-contacting surface the less likely it is that clogging will occur inside the membrane due to the intrusion of the removed material into the membrane.
  • the long diameter/short diameter ratio of the pores on the liquid-contacting surface is, for example, 1.8 or more, 1.82 or more, 1.84 or more, 1.85 or more, 1.9 or more, or 1.95 or more.
  • the long diameter/short diameter ratio of the pores is, for example, 10 or less, 5 or less, 3 or less, or 2.5 or less.
  • the long diameter/short diameter ratio of the pores is, for example, 1.8 to 10, 1.8 to 5, 1.8 to 3, 1.8 to 2.5, 1.85 to 3, 1.85 to 2.5, 1.9 to 3, or 1.9 to 2.5.
  • the greater the anisotropy of the pores on the liquid-contacting surface the less likely the inside of the membrane is to be blocked by the intrusion of the removed material into the membrane.
  • the porous membrane may be a hollow fiber membrane.
  • the porous structure of the hollow fiber membrane may have a substantially homogeneous structure in the membrane thickness direction from the primary side to the secondary side.
  • a substantially homogeneous structure means that the average pore size does not change significantly, and refers to a membrane structure in which the ratio of the maximum value to the minimum value (maximum value/minimum value) when the average pore size is calculated at equal distances from the membrane surface in the membrane thickness direction is 10 or less, 5 or less, or 3 or less.
  • the maximum value/minimum value of the average pore size may be 1 or more, 1.01 or more, or 1.05 or more.
  • the maximum value/minimum value of the average pore size may also be 1 or more and 10 or less, 1 or more and 5 or less, 1 or more and 3 or less, 1.01 or more and 10 or less, 1.01 or more and 5 or less, 1.01 or more and 3 or less, 1.05 ...5 or more and 5 or less, or 1.05 or more and 3 or less.
  • the average pore size of the primary surface in a hollow fiber membrane having a homogeneous structure is, for example, 0.05 ⁇ m or more, 0.1 ⁇ m or more, 0.2 ⁇ m or more, 0.3 ⁇ m or more, 0.4 ⁇ m or more, 0.5 ⁇ m or more, or 0.6 ⁇ m or more.
  • the average pore size is, for example, 10 ⁇ m or less, 5 ⁇ m or less, 1 ⁇ m or less, 0.95 ⁇ m or less, 0.9 ⁇ m or less, 0.85 ⁇ m or less, or 0.8 ⁇ m or less.
  • the average pore size of the primary surface is, for example, 0.05 ⁇ m or more and 10 ⁇ m or less, 0.1 ⁇ m or more and 5 ⁇ m or less, 0.2 ⁇ m or more and 1 ⁇ m or less, 0.3 ⁇ m or more and 0.95 ⁇ m or less, 0.4 ⁇ m or more and 0.9 ⁇ m or less, 0.5 ⁇ m or more and 0.85 ⁇ m or less, or 0.6 ⁇ m or more and 0.8 ⁇ m or less.
  • the blocking pore size of the hollow fiber membrane having a homogeneous structure is, for example, 0.05 ⁇ m or more, 0.1 ⁇ m or more, 0.2 ⁇ m or more, 0.3 ⁇ m or more, 0.4 ⁇ m or more, or 0.5 ⁇ m or more.
  • the blocking pore size of the hollow fiber membrane having a homogeneous structure is, for example, 10 ⁇ m or less, 5 ⁇ m or less, 1 ⁇ m or less, 0.9 ⁇ m or less, 0.8 ⁇ m or less, or 0.7 ⁇ m or less.
  • the blocking pore size of the hollow fiber membrane is, for example, 0.05 ⁇ m to 10 ⁇ m, 0.05 ⁇ m to 5 ⁇ m, 0.05 ⁇ m to 1 ⁇ m, 0.1 ⁇ m to 0.9 ⁇ m, 0.2 ⁇ m to 0.8 ⁇ m, 0.3 ⁇ m to 0.7 ⁇ m, 0.4 ⁇ m to 0.7 ⁇ m, or 0.5 ⁇ m to 0.7 ⁇ m.
  • the blocking pore size is 0.05 ⁇ m or more, it tends to suppress the permeation resistance, suppress the pressure required for filtration, and suppress clogging of the membrane surface due to the destruction and deformation of microbial particles, as well as a decrease in filtration efficiency. Also, if the blocking pore size is 10 ⁇ m or less, sufficient fractionation tends to be obtained.
  • the inner diameter of the hollow portion of the hollow fiber membrane is, for example, 1000 ⁇ m or more, or 1050 ⁇ m or more.
  • the inner diameter of the hollow portion of the hollow fiber membrane is, for example, 3000 ⁇ m or less, 2500 ⁇ m or less, 2000 ⁇ m or less, 1900 ⁇ m or less, 1800 ⁇ m or less, 1700 ⁇ m or less, 1600 ⁇ m or less, or 1500 ⁇ m or less.
  • the inner diameter of the hollow portion of the hollow fiber membrane is, for example, 1000 ⁇ m or more and 3000 ⁇ m or less, 1000 ⁇ m or more and 2500 ⁇ m or less, 1000 ⁇ m or more and 2000 ⁇ m or less, 1100 ⁇ m or more and 1900 ⁇ m or less, or 1200 ⁇ m or more and 1800 ⁇ m or less. If the inner diameter of the hollow portion is 1000 ⁇ m or more, the entrance of the hollow portion tends not to be blocked by cells. If the inner diameter of the hollow portion is 3000 ⁇ m or less, the number of hollow fiber membranes that make up the filtration module increases, the effective membrane area per filtration module increases, and filtration performance tends to be excellent.
  • the membrane thickness of the hollow fiber membrane is, for example, 100 ⁇ m or more, 200 ⁇ m or more, 300 ⁇ m or more, or 400 ⁇ m or more.
  • the membrane thickness of the hollow fiber membrane is, for example, 1400 ⁇ m or less, 1300 ⁇ m or less, 1200 ⁇ m or less, 1100 ⁇ m or less, 1000 ⁇ m or less, 900 ⁇ m or less, 800 ⁇ m or less, 700 ⁇ m or less, 600 ⁇ m or less, or 500 ⁇ m or less.
  • the membrane thickness of the hollow fiber membrane is, for example, 100 ⁇ m or more and 1400 ⁇ m or less, 200 ⁇ m or more and 1200 ⁇ m or less, or 300 ⁇ m or more and 1000 ⁇ m or less. If the membrane thickness is 100 ⁇ m or more, the strength of the hollow fiber membrane tends to be easily maintained. Furthermore, it tends to be easy to maintain an appropriate filtration speed. Furthermore, if the membrane thickness is 1,400 ⁇ m or less, the number of hollow fiber membranes constituting the filtration module increases, the effective cross-sectional area per filtration module increases, and filtration performance tends to be excellent.
  • the hollow fiber membrane is, for example, made of a synthetic polymer membrane.
  • the synthetic polymer is, for example, hydrophobic.
  • An example of a synthetic polymer includes, but is not limited to, polyvinylidene fluoride.
  • the inventors have found that the multiple liquid-contacting surface structures of the third example of the porous membrane affect the filtration performance.
  • each of the multiple liquid-contacting surface structures alone can be sufficiently effective.
  • a synergistic effect can be achieved by combining multiple liquid-contacting surface structures. For example, once the clogging of membrane pores due to the accumulation of removed matter on the membrane surface begins to progress, it is believed to progress at an accelerated rate, using the deposits as a foothold. For this reason, it is effective to use a porous membrane having a liquid-contacting surface that has multiple structural features within an appropriate range.
  • the shear stress due to the flow of the culture solution on the liquid-contacting surface of the porous membrane 112 is set to 4.0 N/m 2 or more.
  • the shear stress may be 4.1 N/m 2 or more, 4.2 N/m 2 or more, 4.3 N/m 2 or more, 4.4 N/m 2 or more, or 4.5 N/m 2 or more.
  • the shear stress may be 50 N/m 2 or less, 30 N/m 2 or less, 20 N/m 2 or less, 15 N/m 2 or less, or 10 N/m 2 or less.
  • the shear stress is 4.0 N/m 2 or more and 50 N/m 2 or less, 4.0 N/m 2 or more and 30 N/m 2 or less, 4.0 N/m 2 or more and 20 N/m 2 or less, 4.0 N/m 2 or more and 15 N/m 2 or less, 4.0 N/m 2 or more and 10 N/m 2 or less, 4.1 N/m 2 or more and 50 N/m 2 or less, 4.2 N/m 2 or more and 30 N/m 2 or less, 4.3 N/m 2 or more and 20 N/m 2 or less, 4.4 N/m 2 or more and 15 N/m 2 or less, 4.5 N/m 2 or more and 50 N/m 2 or less, 4.5 N/m 2 or more and 30 N/m 2 or less, 4.5 N/m 2 or more and 20 N/m 2 or less, 4.5 N/m 2 or more and 15 N/m 2 or less , or 4.5 N/m
  • the shear stress is 4.0 N/m 2 or more and 50 N/m 2
  • porous membrane according to the third example it is possible to suppress a decrease in the permeability of the cell product in the porous membrane 112 by setting the shear stress due to the culture solution on the liquid-contacting surface of the porous membrane 112 to 4.0 N/m2 or more.
  • the shear stress may be measured based on the viscosity of the culture solution, and the flow rate of the culture solution filtered through the porous membrane 112 in a direction parallel to the membrane surface may be controlled so that the measured shear stress is 4.0 N/m 2 or more.
  • the control unit 301 may control the linear velocity of the culture solution flowing through the porous membrane 112 by controlling the pump 123, and control the flow rate of the culture solution filtered through the porous membrane 112 in a direction parallel to the membrane surface so that the shear stress is 4.0 N/m 2 or more.
  • the shear stress SS, the viscosity VC of the culture solution, and the shear rate SV are in the relationship of the above formula (3).
  • the viscosity VC of the culture solution can be obtained in advance. It may be measured by a viscometer provided in the flow path 113.
  • the shear rate SV can be calculated from the linear velocity LV, and the linear velocity LV can be obtained, for example, from the output of the pump 123.
  • the linear velocity LV may be measured by a flow meter provided in the flow path 113.
  • the shear stress SS of the culture solution can be measured based on the known viscosity VC of the culture solution and the obtained linear velocity LV or shear velocity SV of the culture solution.
  • a control unit 301 is connected to the pump 123.
  • the control unit 301 may control the pump 123 to control the linear velocity of the culture solution flowing through the porous membrane 112, thereby controlling the flow rate of the culture solution filtered through the porous membrane 112 in a direction parallel to the membrane surface so that the shear stress is 4.0 N/ m2 or more.
  • the shear stress in the porous membrane 112 is set to 4.0 N/m 2 or more, but this does not exclude the occurrence of a period in which the shear stress in the porous membrane 112 is 4.0 N/m 2 or less. For example, due to a delay in feedback control of the pump, a period in which the shear stress in the porous membrane 112 is 4.0 N/m 2 or less may occur.
  • the shear stress in the porous membrane 112 may be set to 4.0 N/m 2 or more for at least 50% of the entire period in which the cells are cultured.
  • Example 1 A monoclonal antibody-producing Chinese hamster ovary (CHO) cell line (ATCC CRL-12445) was thawed after selecting cells that had been adapted to serum-free medium and suspended and then frozen. The cells were placed in a 125 mL Erlenmeyer flask to which 10 mL of serum-free medium having the composition shown in Table 1 had been dispensed in advance, and the cells and medium were mixed in the Erlenmeyer flask. The cell count was confirmed using a live/dead cell autoanalyzer (Vi-CELL XR, Beckman), and the cells were diluted with medium to a cell density of 3.5 x 105 cells/mL. The cells were then cultured with shaking in an incubator at 37°C in a 5% CO2 atmosphere for 4 days.
  • CHO Chinese hamster ovary
  • 500 mL of the culture solution containing the cells at a density of 3.5 ⁇ 10 5 cells/mL was placed into three new 1 L Erlenmeyer flasks, and the cells were shake-cultured in an incubator at 37° C. and 5% CO 2 for three days.
  • the culture medium containing cells at a density of 1.5 x 107 cells/mL was aseptically removed from the culture tank, and 600 mL was transferred into a spinner flask as a culture tank that had been pre-sterilized by autoclaving.
  • a mini module of porous hollow fiber membranes was prepared, with the effective length adjusted so that the membrane area of the liquid-contacting portion was 3 cm2 .
  • a porous hollow fiber membrane manufactured by Asahi Kasei Medical Co., Ltd., BioOptimal (registered trademark) MF-SL
  • PSf polysulfone
  • the pore size, inner diameter, outer diameter and membrane thickness of the primary side of the BioOptimal MF-SL hollow fiber membrane were measured.
  • the maximum/minimum average pore size in the membrane thickness direction of the hollow fiber membrane was 44.3
  • the spinner flask and the first opening of the hollow part which is the primary side of the porous hollow fiber membrane, were connected by a first flow path, and the second opening of the hollow part of the porous hollow fiber membrane and the spinner flask were connected by a second flow path.
  • the secondary side of the porous hollow fiber membrane and the spinner flask were connected by a third flow path, and the culture medium filtered through the porous hollow fiber membrane was returned to the spinner flask.
  • the ambient temperature of the spinner flask and the porous hollow fiber membrane was set to 4°C, and the culture solution was stirred in the spinner flask.
  • the culture solution was sent from the spinner flask to the porous hollow fiber membrane via the first flow path using a magnetic levitation centrifugal pump (PuraLev i30SU, manufactured by Levitronix), and tangential flow filtration was performed.
  • the culture solution that passed through the hollow part of the porous hollow fiber membrane without being filtered was returned to the spinner flask via the second flow path.
  • the culture solution filtered through the porous hollow fiber membrane was returned to the spinner flask via the third flow path.
  • the first and third flow paths had a structure that made it possible to sample the culture solution inside.
  • TMP transmembrane pressure
  • the culture solution was filtered through BioOptimal MF-SL in the same manner, except that the shear stress was set to 2.06 N/m 2.
  • the shear stress was set to 2.06 N/m 2.
  • the permeability of the monoclonal antibody through BioOptimal MF-SL was 96.5%, and the transmembrane pressure was 2.8 kPa.
  • the culture solution was filtered through BioOptimal MF-SL in the same manner, except that the shear stress was set to 3.09 N/m 2.
  • the shear stress was set to 3.09 N/m 2.
  • the permeability of the monoclonal antibody through BioOptimal MF-SL was 96.3%, and the transmembrane pressure was 4.5 kPa.
  • the culture solution was filtered through BioOptimal MF-SL in the same manner, except that the shear stress was set to 4.58 N/m 2.
  • the shear stress was set to 4.58 N/m 2.
  • the permeability of the monoclonal antibody through BioOptimal MF-SL decreased to 78.8%, and the transmembrane pressure increased to 43.4 kPa.
  • the culture solution was filtered through BioOptimal MF-SL in the same manner, except that the shear stress was set to 9.16 N/m 2.
  • the shear stress was set to 9.16 N/m 2.
  • the permeability of the monoclonal antibody through BioOptimal MF-SL was 78.1%, and the transmembrane pressure was 59.6 kPa.
  • BioOptimal MF-SL is used as the porous hollow fiber membrane, it was shown that if the shear stress is set to 4.0 N/ m2 or less, the permeability of the cell product can be maintained high and the transmembrane pressure difference can be kept low.
  • Example 1 carried out under an atmosphere of 4°C, the activity of cells present in the system was suppressed, so the total amount of cell products was kept constant. In contrast, under conditions in which cells present in the system produce products over time, if the products do not permeate the porous membrane, the products will accumulate in the system over time. Therefore, when the membrane permeation of the cell products is inhibited, the denominator value when calculating the permeability increases, so the permeability of the cell products in the porous membrane is smaller than when the atmospheric temperature is 4°C. Therefore, the difference in permeability in the porous membrane before and after the membrane permeation of the cell products is inhibited is large. Therefore, the difference in permeability before and after the shear stress of 4.0 N/ m2 shown in Example 1 becomes even larger as the atmospheric temperature increases. The same is true for other examples carried out under an atmosphere of 4°C.
  • Example 2 A porous hollow fiber membrane (MICROZA (registered trademark) UMP, manufactured by Asahi Kasei Corporation) having a blocking pore size of 0.2 ⁇ m, made of polyvinylidene fluoride (PVDF), and having a homogeneous structure was prepared.
  • MICROZA registered trademark
  • PVDF polyvinylidene fluoride
  • the maximum/minimum value of the average pore size in the thickness direction of the hollow fiber membrane was 1.5
  • the culture solution was filtered through the porous hollow fiber membrane in the same manner as in Example 1.
  • the permeability of the monoclonal antibody through MICROZA UMP was 97.0%, and the transmembrane pressure difference was 4.7 kPa.
  • Example 3 A porous hollow fiber membrane (MICROZA (registered trademark) UJP, manufactured by Asahi Kasei Corporation) having a blocking pore size of 0.65 ⁇ m, made of polyvinylidene fluoride (PVDF), and having a homogeneous structure was prepared.
  • MICROZA registered trademark
  • UJP porous hollow fiber membrane
  • PVDF polyvinylidene fluoride
  • the maximum/minimum value of the average pore size in the thickness direction of the hollow fiber membrane was 2.0
  • the culture solution was filtered through the porous hollow fiber membrane in the same manner as in Example 1.
  • the shear stress was set to 1.15 N/ m2 and 300 L/ m2 of the culture solution was filtered through MICROZA UJP
  • the permeability of the monoclonal antibody through MICROZA UJP was 95.7%
  • the transmembrane pressure difference was 1.2 kPa.
  • the monoclonal antibody permeability through the MICROZA UJP was 99.4%, and the transmembrane pressure difference was 1.0 kPa.
  • a porous hollow fiber membrane having a blocking pore size of 0.2 ⁇ m, made of polyethersulfone (PES), and having a symmetrical gradient structure (Repligen, F2: taken from RF02PES) was prepared.
  • the symmetrical gradient structure is a structure in which the porous structure of the hollow fiber membrane has an average pore size that increases from the primary side to the secondary side in the membrane thickness direction and then decreases to the same size as the primary side.
  • the maximum/minimum average pore size in the thickness direction of the hollow fiber membrane was 13.3
  • the culture solution was filtered through the porous hollow fiber membrane in the same manner as in Example 1.
  • the shear stress was set to 4.58 N/ m2 and 300 L/ m2 of culture solution was filtered through the hollow fibers manufactured by Repligen
  • the permeability of the monoclonal antibody through the hollow fibers manufactured by Repligen was 86.4%
  • the transmembrane pressure difference was 1.0 kPa.
  • FIG. 2 A porous hollow fiber membrane (manufactured by Cytiva, taken from CFP-4-E-5A) having a blocking pore size of 0.45 ⁇ m and made of polysulfone (PSf) and having a symmetrical inclined structure was prepared.
  • the culture solution was filtered through the porous hollow fiber membrane in the same manner as in Example 1.
  • the shear stress was set to 4.58 N/ m2 and 300 L/ m2 of culture solution was filtered through the hollow fibers manufactured by Cytiva
  • the permeability of the monoclonal antibody through the hollow fibers manufactured by Cytiva was 80.6%
  • the transmembrane pressure difference was 2.0 kPa.
  • Example 4 A monoclonal antibody-producing Chinese hamster ovary (CHO) cell line (ATCC CRL-12445) was thawed after selecting cells that had been adapted to serum-free medium and suspended, and then the cells were placed in a 125 mL Erlenmeyer flask to which 10 mL of serum-free medium having the composition shown in Table 1 had been dispensed in advance, and the cells and medium were mixed in the Erlenmeyer flask. The cell count was confirmed using a live/dead cell autoanalyzer (Vi-CELL XR, Beckman), and the cells were diluted with medium to a cell density of 3.5 x 105 cells/mL. The cells were then cultured with shaking in an incubator at 37°C in a 5% CO2 atmosphere for 4 days.
  • CHO Chinese hamster ovary
  • Fresh medium was aseptically pumped from a 50 L bag (Thermo Fisher, Productainer BioProcess Container (BPC), 50 L) to the culture tank in an amount equal to the amount of culture solution extracted from the culture tank by filtration, and the amount of culture solution in the culture tank was controlled to be constant.
  • the medium exchange rate of the culture solution was set to 1 vvd -1 (vessel volumes per day), and when the glucose concentration became 1 g/L or less or the glutamine concentration became 1 mmol/L or less, the medium exchange rate of the culture solution was increased by 0.5 vvd -1 min.
  • the culture solution containing cells at a density of 1 x 10 8 cells/mL was aseptically collected, and 600 mL of the culture solution was transferred into a spinner flask as a culture tank that had been sterilized by autoclaving in advance.
  • a mini module of a porous hollow fiber membrane (MICROZA (registered trademark) UMP, manufactured by Asahi Kasei) was prepared, with the effective length adjusted so that the membrane area of the liquid-contacting part was 3 cm 2.
  • the first opening of the hollow part which is the primary side of the spinner flask and the porous hollow fiber membrane, was connected by a first flow path
  • the second opening of the hollow part of the porous hollow fiber membrane and the spinner flask were connected by a second flow path
  • the secondary side of the porous hollow fiber membrane and the spinner flask were connected by a third flow path.
  • the ambient temperature of the spinner flask and the porous hollow fiber membrane was set to 4°C, and the culture solution was stirred in the spinner flask.
  • the culture solution was sent from the spinner flask to the porous hollow fiber membrane via the first flow path using a magnetic levitation centrifugal pump (PuraLev i30SU, manufactured by Levitronix), and tangential flow filtration was performed.
  • the culture solution that passed through the hollow part of the porous hollow fiber membrane without being filtered was returned to the spinner flask via the second flow path.
  • the culture solution filtered through the porous hollow fiber membrane was returned to the spinner flask via the third flow path.
  • the first and third flow paths had a structure that made it possible to sample the culture solution inside.
  • TMP transmembrane pressure
  • the culture solution was filtered through MICROZA UMP in the same manner, except that the shear stress was set to 3.04 N/m 2.
  • the shear stress was set to 3.04 N/m 2.
  • the monoclonal antibody permeability through MICROZA UMP was 96.1% and the transmembrane pressure was 8.2 kPa
  • the monoclonal antibody permeability through MICROZA UMP was 94.2% and the transmembrane pressure was 21.5 kPa.
  • the culture solution was filtered through MICROZA UMP in the same manner, except that the shear stress was set to 4.56 N/ m2 .
  • the shear stress was set to 4.56 N/ m2 .
  • the permeability of the monoclonal antibody through MICROZA UMP decreased to 95.5%, and the transmembrane pressure was 5.1 kPa.
  • the culture solution was filtered through MICROZA UMP in the same manner, except that the shear stress was set to 6.76 N/ m2 .
  • the shear stress was set to 6.76 N/ m2 .
  • the permeability of the monoclonal antibody through MICROZA UMP was 96.1%, and the transmembrane pressure was 12.0 kPa.
  • Example 5 Except for using MICROZA UJP as the porous hollow fiber membrane, the culture solution was filtered through the porous hollow fiber membrane in the same manner as in Example 4. As shown in Figures 11 and 12, when the shear stress was set to 1.69 N/ m2 and 300 L/ m2 of culture solution was filtered through MICROZA UJP, the permeability of the monoclonal antibody through MICROZA UJP was 94.4%, and the transmembrane pressure difference was 1.2 kPa.
  • the monoclonal antibody permeability through the MICROZA UJP was 94.3%, and the transmembrane pressure difference was 1.2 kPa.
  • Example 3 Except for using the same hollow fiber membrane manufactured by Repligen as in Comparative Example 1 as the porous hollow fiber membrane, the culture solution was filtered through the porous hollow fiber membrane in the same manner as in Example 4. As shown in Figures 11 and 12, when the shear stress was set to 1.69 N/ m2 and 300 L/ m2 of culture solution was filtered through the hollow fiber membrane manufactured by Repligen, the monoclonal antibody permeability through the hollow fiber membrane manufactured by Repligen was 91.1%, and the transmembrane pressure difference was 1.2 kPa.
  • Example 4 Except for using the same hollow fiber membrane manufactured by Cytiva as in Comparative Example 2, the culture solution was filtered through the porous hollow fiber membrane in the same manner as in Example 4. As shown in Figures 11 and 12, when the shear stress was set to 1.69 N/ m2 and 300 L/ m2 of culture solution was filtered through the hollow fiber membrane manufactured by Cytiva, the permeability of the monoclonal antibody through the hollow fiber membrane manufactured by Cytiva was 86.5%, and the transmembrane pressure difference was 0.7 kPa.
  • Example 6 A monoclonal antibody-producing Chinese hamster ovary (CHO) cell line (ATCC CRL-12445) was thawed after selecting cells that had been adapted to serum-free medium and suspended, and then the cells were placed in a 125 mL Erlenmeyer flask to which 10 mL of serum-free medium having the composition shown in Table 1 had been dispensed in advance, and the cells and medium were mixed in the Erlenmeyer flask. The cell count was confirmed using a live/dead cell autoanalyzer (Vi-CELL XR, Beckman), and the cells were diluted with medium to a cell density of 3.5 x 105 cells/mL. The cells were then cultured with shaking in an incubator at 37°C in a 5% CO2 atmosphere for 4 days.
  • CHO Chinese hamster ovary
  • a 1.28 L culture solution containing cells at a density of 5.5 x 105 cells/mL was aseptically placed in a 3 L culture tank previously sterilized by autoclaving.
  • the cells were cultured with stirring for 3 days under a 5% CO2 atmosphere at 37°C while blowing in oxygen so that the DO did not fall below 70%.
  • a module of porous hollow fiber membranes (Asahi Kasei, Microza UMP) was prepared, the number and effective length of which were adjusted so that the membrane area of the liquid-contacting part was 200 cm2 .
  • the first opening of the hollow part which is the primary side of the culture tank and the porous hollow fiber membrane, was connected by a first flow path, and the second opening of the hollow part of the porous hollow fiber membrane and the culture tank were connected by a second flow path.
  • the culture solution filtered by the porous hollow fiber membrane was not returned to the culture tank.
  • the culture tank was provided with an outlet for sampling the internal medium and a supply port for supplying fresh medium.
  • the ambient temperature of the culture tank and the porous hollow fiber membrane was set to 37°C, and the culture solution was stirred in the culture tank.
  • the culture solution was sent from the culture tank to the porous hollow fiber membrane via the first flow path using a magnetic levitation centrifugal pump (PuraLev 200MU, manufactured by Levitronix), and tangential flow filtration was performed.
  • the culture solution that passed through the hollow part of the porous hollow fiber membrane without being filtered by the porous hollow fiber membrane was returned to the culture tank via the second flow path.
  • oxygen was introduced into the culture tank using a sparger.
  • air containing carbon dioxide at a concentration of 5% was constantly introduced into the culture tank.
  • Fresh medium was aseptically pumped from a 20 L bag (Thermo Fisher, Productainer BioProcess Container (BPC), 20 L) to the culture tank in an amount equal to the amount of culture solution extracted from the culture tank by filtration, and the amount of culture solution in the culture tank was controlled to be constant.
  • the medium exchange rate of the culture solution was set to 1 vvd -1 (vessel volumes per day), and when the glucose concentration became 1 g/L or less or the glutamine concentration became 1 mmol/L or less, the medium exchange rate of the culture solution was increased by 0.375 vvd -1 min.
  • a single-use manometer (PENDOTECH, PREPS-N-038) was installed on the primary and secondary sides of the porous hollow fiber membrane, and the transmembrane pressure (TMP) was measured over time.
  • TMP transmembrane pressure
  • the amount of culture solution sent from the culture tank to the porous hollow fiber membrane was set so that the shear stress on the inner surface of the porous hollow fiber membrane was 2.10 N/m 2.
  • the filtration flow rate in the porous hollow fiber membrane was increased stepwise by a pump to 1.0 LMH, 1.5 LMH, 2.0 LMH, 2.5 LMH, and 3.0 LMH, so that the amount of fresh medium introduced was increased to adjust the glucose concentration and glutamine concentration in accordance with the increase in cells.
  • the cells were bled so that the density of the cells in the culture solution in the culture tank was 7.5 x 10 7 cells/mL. After the start of breeding, the actual cell density was in the range of 6.5 ⁇ 10 7 cells/mL or more and 9.3 ⁇ 10 7 cells/mL or less. Furthermore, a liquid level sensor was placed in the culture tank, and fresh medium in the same amount as the bled culture solution was introduced into the culture tank to keep the liquid level constant.
  • the culture medium was sampled before and after filtration once or twice a day, and the antibody concentration in the culture medium was measured. The same experiment was repeated twice, and as shown in Figures 13 and 14, when the shear stress was set to 2.10 N/ m2 and 300 L/ m2 of culture medium was filtered through the MICROZA UMP, the monoclonal antibody permeability through the MICROZA UMP was 98.7% and 98.1%, respectively, and the transmembrane pressure difference was 7.3 kPa and 4.8 kPa, respectively.
  • the analytical methods used in the above-mentioned Examples, Comparative Examples, and Reference Examples are described below.
  • the density and viability of cells contained in the culture medium were measured using a live/dead cell autoanalyzer (Vi-CELL XR manufactured by Beckman Coulter).
  • the sample was diluted with PBS (-) (Fujifilm Wako) and 600 ⁇ L was used for analysis.
  • the image analysis method used was "CHO" in Vi-CELL XR, and the settings of Minimum diameter ( ⁇ m), Cell Brightness (%), and Viable cell spot Brightness (%) were changed appropriately to suit the actual situation.
  • the antibody concentration was measured by HPLC using the following method.
  • Detector ultraviolet spectrophotometer (measurement wavelength: 280 nm)
  • Column POROS G 20 ⁇ m Column, 4.6 ⁇ 50 mm, 0.8 mL (ThermoFisher)
  • Column temperature room temperature (4)
  • Mobile phase Mobile phase A: 7.098 g of disodium hydrogen phosphate (anhydrous) and 8.766 g of sodium chloride were dissolved in 800 mL of water, and 1 mol/L hydrochloric acid was added to adjust the pH to 7.0, and water was added to make 1000 mL.
  • Mobile phase B 12 mL of 1 mol/L hydrochloric acid and 8.766 g of sodium chloride were dissolved in water to make 1000 mL.
  • Delivery of Mobile Phase The mobile phases were delivered at a flow rate of 2 mL/min, with the ratio of mobile phase A to mobile phase B being changed as shown in the table below.
  • the cell culture fluid was centrifuged at 300 x g for 2 to 5 minutes, and the supernatant was sampled.
  • nine serial dilutions of commercially available human immunoglobulin G (Japan Blood Products Organization, Donated Blood Venoglobulin IH 5% Intravenous Injection 2.5 g/50 mL) and the cell culture fluid supernatant were delivered using the above procedure.
  • a standard curve was created using nine peak areas of human immunoglobulin G, and the antibody concentration in each solution was calculated from the standard curve and the peak area of the sample.
  • the viscosity of the culture medium was measured using an EMS viscometer (EMS-1000S, manufactured by Kyoto Electronics Manufacturing Co., Ltd.). A 300 ⁇ L sample was placed in a dedicated standard sample container together with a ⁇ 1.5 mm spherical probe and analyzed. The motor speed was set to 400 rpm, and after a holding time of 30 seconds, measurements were taken 10 times with a measurement time of 1 second. The average value of the 10 measurements was used as the viscosity of the culture medium.
  • EMS viscometer EMS-1000S, manufactured by Kyoto Electronics Manufacturing Co., Ltd.
  • 111 culture tank
  • 112 porous membrane
  • 113, 114, 115, 116, 117, 118, 119 flow path, 123, 125, 126, 133, 134, 135: pump

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PCT/JP2023/040994 2022-11-15 2023-11-14 細胞産生物の製造方法、細胞産生物の精製方法、細胞産生物の膜透過率の低下を抑制する方法、細胞産生物の製造システム、及び細胞産生物の精製システム Ceased WO2024106441A1 (ja)

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US19/129,866 US20260062664A1 (en) 2022-11-15 2023-11-14 Method for producing product by cells, method for purifying product produced by cells, method for suppressing decrease in membrane permeability of product produced by cells, system for producing product by cells, and system for purifying product produced by cells
EP23891588.8A EP4621062A1 (en) 2022-11-15 2023-11-14 Method for producing cell product, method for purifying cell product, method for suppressing decrease in membrane permeability of cell product, system for producing cell product, and system for purifying cell product
EP25203403.8A EP4647486A3 (en) 2022-11-15 2023-11-14 Method for producing cell product, method for purifying cell product, method for suppressing decrease in membrane permeability of cell product, system for producing cell product, and system for purifying cell product
KR1020257014206A KR20250078532A (ko) 2022-11-15 2023-11-14 세포 산생물의 제조 방법, 세포 산생물의 정제 방법, 세포 산생물의 막 투과율의 저하를 억제하는 방법, 세포 산생물의 제조 시스템 및 세포 산생물의 정제 시스템
CN202380077340.1A CN120153085A (zh) 2022-11-15 2023-11-14 细胞产物的制造方法、细胞产物的纯化方法、抑制细胞产物的膜透过率降低的方法、细胞产物的制造系统及细胞产物的纯化系统
KR1020257014205A KR20250078531A (ko) 2022-11-15 2023-11-14 세포 산생물의 제조 방법, 세포 산생물의 정제 방법, 세포 산생물의 막 투과율의 저하를 억제하는 방법, 세포 산생물의 제조 시스템 및 세포 산생물의 정제 시스템
KR1020257014171A KR20250078526A (ko) 2022-11-15 2023-11-14 세포 산생물의 제조 방법, 세포 산생물의 정제 방법, 세포 산생물의 막 투과율의 저하를 억제하는 방법, 세포 산생물의 제조 시스템 및 세포 산생물의 정제 시스템
JP2024558901A JPWO2024106441A1 (https=) 2022-11-15 2023-11-14
EP25203439.2A EP4644526A3 (en) 2022-11-15 2023-11-14 Method for producing cell product, method for purifying cell product, method for suppressing decrease in membrane permeability of cell product, system for producing cell product, and system for purifying cell product
US19/233,489 US20250361289A1 (en) 2022-11-15 2025-06-10 Method for producing product by cells, method for purifying product produced by cells, method for suppressing decrease in membrane permeability of product produced by cells, system for producing product by cells, and system for purifying product produced by cells
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