Integrity test method for membrane module internally containing porous membrane

Abstract

The present invention is an integrity test method for a membrane module that internally contains a porous membrane having a first surface and a second surface opposite from the first surface, the method including: filling a space in the membrane module in contact with at least the second surface of the porous membrane with a liquid; removing the liquid with which the space in the membrane module in contact with the second surface of the porous membrane is filled; and pressurizing the first surface of the damp porous membrane with a gas and measuring the gas diffusion flow rate of the porous membrane.

Description

Integrity testing method for membrane modules containing porous membranes

[0001] The present invention relates to a method for testing the integrity of a membrane module containing a porous membrane.

[0002] In the manufacturing process of biological products such as plasma-derived products and biopharmaceuticals, virus removal / inactivation steps are incorporated to improve safety against viruses. Among these, virus removal by filtration using porous membranes is an effective method for reducing viruses without denaturing useful proteins. In virus removal by filtration using porous membranes, a non-destructive integrity test of the membrane module is required to ensure the safety of the manufactured pharmaceutical product, confirming that the virus removal membrane functioned effectively during the virus removal process. The same applies when the membrane is used for other purposes (see, for example, Patent Documents 1 to 5).

[0003] There are several methods for testing the integrity of a membrane, one of which involves measuring the gas diffusion rate through the membrane. The gas diffusion rate is the flow rate of gas per unit time through a membrane that is wet with a liquid. When a gas pressure lower than the bubble point is applied to a wet membrane, the liquid in the membrane's pores does not move, maintaining a blocked state. However, according to Henry's Law, the gas dissolves in the liquid within the pores. Therefore, the gas dissolved in the liquid at the pore entrance diffuses to the pore exit and vaporizes.

[0004] The gas diffusion flow rate Q through the membrane is given by the following equation: Q = DHPSφC / L where D represents the diffusion coefficient of the gas in the liquid, H represents the solubility of the gas in the liquid, P represents the pressure difference between the first and second surfaces of the membrane, S represents the surface area of ​​the membrane, φ represents the porosity of the membrane, C represents a coefficient that depends on the structure of the membrane, and L represents the thickness of the membrane.

[0005] When defects such as pinholes occur in a membrane, the gas diffusion flow rate through the membrane increases. It has been reported that measuring the gas diffusion flow rate through a membrane is difficult when the membrane area is small, but easy when the membrane area is large (see, for example, Patent Document 6).

[0006] Japanese Patent Publication No. 2005-40756, International Publication No. 2012 / 147850, Japanese Patent Publication No. 2013-505824, International Publication No. 2019 / 066061, International Publication No. 2022 / 118943, Japanese Patent No. 5037758

[0007] One of the objectives of this invention is to provide highly accurate integrity testing for porous membranes.

[0008] [1] A method for testing the integrity of a membrane module containing a porous membrane having a first surface and a second surface opposite to the first surface, comprising: filling a space in the membrane module that is in contact with at least the second surface of the porous membrane with a liquid; removing the liquid filled in the space in contact with the second surface of the porous membrane in the membrane module; and pressurizing the first surface of the wet porous membrane with a gas and measuring the gas diffusion flow rate of the porous membrane.

[0009] [2] The method according to [1], wherein liquid is filled into the space in contact with the first surface of the porous membrane, and the liquid is passed from the first surface to the second surface of the porous membrane to fill the space in contact with the second surface of the porous membrane in the membrane module.

[0010] [3] The method according to [2], further comprising removing the liquid from the space in contact with the first surface of the porous membrane while the space in contact with the second surface of the porous membrane in the membrane module remains filled with liquid.

[0011] [4] The method according to [3], wherein a liquid is dropped out of the membrane module by gravity from a space in contact with the first surface of the porous membrane.

[0012] [5] The method according to [3] or [4], further comprising filling the space in contact with the second surface of the porous membrane within the membrane module with liquid and flowing a gas through the space in contact with the first surface of the porous membrane.

[0013] [6] The method according to [5], wherein liquid is removed from the first surface of a porous membrane by flowing a gas through the space in contact with the first surface of the porous membrane.

[0014] [7] The method according to any one of [1] to [6], comprising filling a space in contact with the first surface of the porous membrane with a liquid, removing the liquid filled in the space in contact with the first surface of the porous membrane, and pressurizing the first surface of the porous membrane with gas after the liquids filled in the space in contact with the first surface and the space in contact with the second surface have been removed and before pressurizing for measuring the gas diffusion flow rate of the porous membrane.

[0015] [8] A method according to any one of [1] to [7] for measuring the gas diffusion flow rate of a porous membrane based on fluctuations in the pressure applied to the first surface of the porous membrane.

[0016] [9] The method according to any one of [1] to [7] for measuring the gas diffusion flow rate of a porous membrane based on the pressure fluctuations of the space in contact with the second surface of the porous membrane.

[0017]

[10] A method according to any one of [1] to [7] for measuring the gas diffusion flow rate of a porous membrane based on the amount of gas used to maintain a constant pressure on the first surface of the porous membrane.

[0018]

[11] The method according to any one of [1] to

[10] , wherein the porous membrane comprises at least one selected from regenerated cellulose, polyvinylidene fluoride, hydrophilic monomer, polystyrene polymer, and hydrophilic polymer.

[0019]

[12] The membrane area of ​​the porous membrane is 0.01 m² ２ 4.0m ２ The method described in any of the following [1] to

[11] .

[0020]

[13] The method according to any one of [1] to

[12] , wherein the pressure applied to the first surface of the porous membrane is 34.5 kPa or more and 343 kPa or less.

[0021]

[14] The method according to any one of [1] to

[13] , wherein the parvovirus removal rate (LRV) of the porous membrane is 4.0 or higher.

[0022]

[15] The method according to any one of [1] to

[14] , wherein after removing the liquid filling the space in contact with the second surface of the porous membrane in the membrane module, the first surface of the porous membrane is pressurized with gas while the second surface of the porous membrane is covered with a film of liquid, and the gas diffusion flow rate of the porous membrane is measured.

[0023]

[16] The method according to any one of [1] to

[15] , wherein after removing the liquid filling the space in contact with the second surface of the porous membrane in the membrane module, the first surface of the porous membrane is pressurized with gas within 24 hours and the gas diffusion flow rate of the porous membrane is measured.

[0024]

[17] The method according to any one of [1] to

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

[0025]

[18] The method according to

[17] , wherein the inner surface of the porous hollow fiber membrane is the first surface and the outer surface of the porous hollow fiber membrane is the second surface.

[0026] According to the present invention, a highly accurate integrity test for porous membranes is provided.

[0027] This is a schematic cross-sectional view of the porous membrane according to this embodiment. This is a schematic graph showing the relationship between the pinhole diameter of the porous membrane and the gas diffusion flow rate. This is a schematic graph showing the relationship between the pinhole diameter of the porous membrane and the virus removal rate (LRV). This is a flowchart showing the integrity test method for a membrane module containing the porous membrane according to this embodiment. This is a table showing the results of the integrity test method for the membrane module according to the example. This is a table showing the results of the integrity test method for the membrane module according to the example. This is a table showing the results of the integrity test method for the membrane module according to the comparative example. This is a table showing the results of the integrity test method for the membrane module according to the comparative example.

[0028] The present invention will be described in detail below with reference to specific embodiments (hereinafter referred to as "these embodiments"). However, the present invention is not limited to the following embodiments and can be implemented in any form without departing from the spirit of the invention.

[0029] A method for testing the integrity of a membrane module containing a porous membrane having a first surface and a second surface facing the first surface according to this embodiment includes filling a liquid into at least the space in contact with the second surface of the porous membrane in the membrane module, removing the liquid filled in the space in contact with the second surface of the porous membrane in the membrane module, pressurizing the first surface of the wet porous membrane with a gas (first pressurization), and measuring the gas diffusion flow rate of the porous membrane. Examples of the porous membrane include a porous flat membrane or a porous hollow fiber membrane. The porous membrane is preferably a porous hollow fiber membrane. Hereinafter, the porous hollow fiber membrane may be simply referred to as a hollow fiber membrane.

[0030] Hereinafter, an example will be described in which the porous membrane is a porous hollow fiber membrane, the inner peripheral surface of the porous hollow fiber membrane is the first surface of the porous hollow fiber membrane, and the outer peripheral surface of the porous hollow fiber membrane is the second surface of the porous hollow fiber membrane. In the present disclosure, the first surface of the porous membrane refers to the surface on the side where the gas is pressurized in the integrity test, and the second surface of the porous membrane refers to the surface on the side where the pressurized air is discharged.

[0031] Hereinafter, an example in which the membrane module contains a plurality of hollow fiber membranes will be described, but the number of hollow fiber membranes contained in the membrane module is not limited and may be one. For example, as shown in FIG. 1, a membrane module 1 according to this embodiment includes a cylindrical container 2, a plurality of hollow fiber membranes 3 disposed in the cylindrical container 2, a first holding member 4A for holding one end of the plurality of hollow fiber membranes 3 at one end of the cylindrical container 2, a second holding member 4B for holding the hollow fiber membranes 3 at the other end of the cylindrical container 2, a first header 5A covering one end of the cylindrical container 2, and a second header 5B covering the other end of the cylindrical container 2.

[0032] The first holding member 4A holds one end of the bundle of the plurality of hollow fiber membranes 3 at one end of the cylindrical container 2. The first holding member 4A embeds the outside of each one end of the plurality of hollow fiber membranes 3 and fills the space between the plurality of hollow fiber membranes 3. The first holding member 4A blocks the space 20 outside the hollow fiber membranes 3 in the cylindrical container 2 and the space 50A in the first header 5A.

[0033] The second holding member 4B holds the other ends of the bundles of the plurality of hollow fiber membranes 3 at the other end of the cylindrical container 2. The second holding member 4B embeds the outside of each of the other ends of the plurality of hollow fiber membranes 3 and fills the space between the plurality of hollow fiber membranes 3. The second holding member 4B blocks the space 20 outside the hollow fiber membranes 3 in the cylindrical container 2 and the space 50B in the second header 5B.

[0034] The cylindrical container 2 is provided with one or more ports 21A, 21B. The ports 21A, 21B communicate with the space 20 outside the hollow fiber membranes 3 in the cylindrical container 2. It is possible to introduce a fluid from outside the cylindrical container 2 into the space 20 in contact with the second surface of the hollow fiber membranes 3 in the cylindrical container 2 using at least one of the ports 21A, 21B. Also, it is possible to discharge a fluid from the space 20 in contact with the second surface of the hollow fiber membranes 3 in the cylindrical container 2 to the outside of the cylindrical container 2 using at least one of the ports 21A, 21B.

[0035] Flow paths can be connected to each of the ports 21A, 21B. Each of the ports 21A, 21B can be closed with a cap or the like. Also, the flow paths connected to each of the ports 21A, 21B can be closed with a valve or the like.

[0036] The first header 5A is provided with an opening 51A. The second header 5B is provided with an opening 51B. The fluid injected into the space 5OB in the second header 5B from the opening 51B of the second header 5B passes through the internal space which is the space in contact with the first surface of the hollow fiber membranes 3, passes through the space 50A in the first header 5A, and is discharged from the opening 51A of the first header 5A. Also, a part of the fluid passing through the inside of the hollow fiber membranes 3 passes from the first surface to the second surface of the membrane portion of the hollow fiber membranes 3 and is discharged into the space 20 in contact with the second surface of the hollow fiber membranes in the cylindrical container 2.

[0037] A flow path can be connected to each of the openings 51A of the first header 5A and the openings 51B of the second header 5B. Each of the openings 51A of the first header 5A and the openings 51B of the second header 5B can be closed with a cap or the like. The flow paths connected to each of the openings 51A of the first header 5A and the openings 51B of the second header 5B can be closed with a valve or the like.

[0038] The outer diameter in the cross-sectional direction of each of the hollow fiber membranes 3 is, for example, 150 μm or more and 700 μm or less, 200 μm or more and 600 μm or less, or 250 μm or more and 450 μm or less. The inner diameter in the cross-sectional direction of each of the hollow fiber membranes 3 is, for example, 100 μm or more and 600 μm or less, 150 μm or more and 500 μm or less, or 200 μm or more and 400 μm or less. The membrane thickness in the cross-sectional direction of each of the hollow fiber membranes 3 is, for example, 20 or more and 100 or less, 30 or more and 90 or less, or 40 μm or more and 60 μm or less. The length in the longitudinal direction of each of the hollow fiber membranes 3 is, for example, 200 mm or more and 400 mm or less, 250 mm or more and 350 mm or less, or 270 mm or more and 300 mm or less. The total membrane area of the plurality of hollow fiber membranes 3 in the membrane module is, for example, 0.01 m ２ or more and 4.0 m ２ or less, 0.01 m ２ or more and 2.0 m ２ or less, 0.01 m ２ or more and 1.5 m ２ or less, 0.01 m ２ or more and 1.0 m ２ or less, 0.03 m ２ or more and 4.0 m ２ or less, 0.03 m ２ or more and 1.0 m ２ or less, or 0.03 m ２ or more and 0.3 m ２ or less. The total area in the case where the number of hollow fiber membranes is 1 is the same.

[0039] Examples of the material of the hollow fiber membrane 3 include regenerated cellulose, polyvinylidene fluoride, polystyrene-based polymers, hydrophilic monomers, and hydrophilic polymers.

[0040] Hollow fiber membranes made from regenerated cellulose are hydrophilic, thus suppressing the adsorption of proteins onto the membrane. Regenerated cellulose is cellulose that has been dissolved by chemical treatment and then regenerated by another chemical treatment. For example, regenerated cellulose can be produced from a copper ammonia cellulose solution. Alternatively, regenerated cellulose can be produced by saponifying cellulose acetate with alkali.

[0041] Polyvinylidene fluoride exhibits excellent heat resistance and moldability. An example of polyvinylidene fluoride is a homopolymer of vinylidene fluoride (VDF). Another example of polyvinylidene fluoride is a copolymer of one or two monomers selected from the group consisting of hexafluoropropylene (HFP), pentafluoropropylene (PFP), tetrafluoroethylene (TFE), chlorotrifluoroethylene (CTFE), and perfluoromethyl vinyl ether (PFMVE), and vinylidene fluoride (VDF).

[0042] Polystyrene polymers exhibit excellent rigidity and moldability. An example of a polystyrene polymer is styrene-divinylbenzene copolymer.

[0043] If the main material of the hollow fiber membrane 3 is hydrophobic, the hollow fiber membrane 3 may be made hydrophilic by a hydrophilic monomer. A hydrophilic monomer is, for example, a hydrophilic vinyl monomer. The hydrophilic vinyl monomer may be bonded to the surface of the hollow fiber membrane 3 by a graft reaction. Examples of hydrophilic vinyl monomers include vinyl monomers having hydroxyl groups such as hydroxypropyl acrylate and hydroxybutyl acrylate, vinyl monomers having amide bonds such as vinylpyrrolidone, vinyl monomers having amino groups such as acrylamide, vinyl monomers having polyethylene glycol chains such as polyethylene glycol monoacrylate, vinyl monomers having anion exchange groups such as triethylammonium ethyl methacrylate, and vinyl monomers having cation exchange groups such as sulfopropyl methacrylate.

[0044] If the main material of the hollow fiber membrane 3 is hydrophobic, the hollow fiber membrane 3 may be coated on its surface with a hydrophilic polymer. The hydrophilic polymer may contain, for example, 2-hydroxyethyl methacrylate or 2-methacryloyloxyethyl phosphorylcholine. An example of a hydrophilic polymer containing 2-hydroxyethyl methacrylate or 2-methacryloyloxyethyl phosphorylcholine is a copolymer of a homopolymer of 2-hydroxyethyl methacrylate or 2-methacryloyloxyethyl phosphorylcholine. Another example of a hydrophilic polymer containing 2-hydroxyethyl methacrylate or 2-methacryloyloxyethyl phosphorylcholine is a random copolymer, graft copolymer, or block copolymer of a hydrophobic monomer such as styrene, ethylene, propylene, propyl methacrylate, butyl methacrylate, ethylhexyl methacrylate, octadecyl methacrylate, benzyl methacrylate, or methoxyethyl methacrylate with a hydrophilic monomer such as 2-hydroxyethyl methacrylate or 2-methacryloyloxyethyl phosphorylcholine. There are no limitations on the method for forming a coating layer on a hollow fiber membrane with a hydrophilic polymer. For example, the hollow fiber may be immersed in a coating solution containing a hydrophilic polymer, and then the coating solution may be removed as appropriate.

[0045] The purpose of filtration by the hollow fiber membrane 3 is not particularly limited, but one example is virus removal. When the use of the hollow fiber membrane 3 is virus removal, the parvovirus removal rate (LRV) of the hollow fiber membrane 3 is, for example, 4.0 or higher, 4.5 or higher, or 5.0 or higher.

[0046] The integrity of the hollow fiber membrane 3 means that the hollow fiber membrane 3 is free from defects to a degree that does not pose a practical problem. The integrity test of the hollow fiber membrane 3 is a test to check whether or not the hollow fiber membrane 3 has defects. The integrity test of the hollow fiber membrane 3 is generally performed before and after filtration with the hollow fiber membrane 3. The absence of defects in the hollow fiber membrane 3 means, for example, that the hollow fiber membrane 3 does not have pinholes.

[0047] The gas diffusion flow rate of the hollow fiber membrane 3 is the flow rate of gas per unit time through the liquid-moistened hollow fiber membrane 3. Examples of liquids include water, ethanol, butanol, propanol, and methanol, as well as mixtures of at least two of these. Examples of gases include air, oxygen, and nitrogen.

[0048] When a gas pressure lower than the bubble point is applied to a moist hollow fiber membrane 3, the liquid in the pores of the hollow fiber membrane 3 does not move and maintains a blocked state. However, according to Henry's law, the gas dissolves in the liquid in the pores. Therefore, the gas dissolved in the liquid at the pore entrance diffuses to the pore exit and vaporizes. The gas diffusion flow rate Q of the hollow fiber membrane 3 is given by the following equation: Q = DHPSφC / L Here, D represents the diffusion coefficient of the gas in the liquid. H represents the solubility of the gas in the liquid. P represents the pressure difference between the first and second surfaces of the hollow fiber membrane 3. S represents the surface area of ​​the hollow fiber membrane 3. φ represents the porosity of the hollow fiber membrane 3. C represents a coefficient that depends on the structure of the hollow fiber membrane 3, such as its curvature. L represents the thickness of the hollow fiber membrane 3.

[0049] As schematically shown in Figure 2, an increase in defects in the hollow fiber membrane 3 tends to increase the gas diffusion flow rate of the hollow fiber membrane 3. Also, as schematically shown in Figure 3, an increase in defects in the hollow fiber membrane 3 tends to increase the leakage of viruses that should be removed by filtration by the hollow fiber membrane 3, and the virus removal rate (LRV) tends to decrease. Therefore, by obtaining the correlation between the gas diffusion flow rate of the hollow fiber membrane 3 and the virus removal rate (LRV) in advance, it is possible to estimate the virus removal rate (LRV) of the hollow fiber membrane 3 from the measured gas diffusion flow rate of the hollow fiber membrane 3. Furthermore, if the gas diffusion flow rate of the hollow fiber membrane 3 is below a predetermined threshold, it is possible to determine that the hollow fiber membrane 3 is usable, and if the gas diffusion flow rate of the hollow fiber membrane 3 is greater than the predetermined threshold, it is possible to determine that the hollow fiber membrane 3 is unusable.

[0050] The gas diffusion flow rate of the hollow fiber membrane 3 is measured, for example, based on fluctuations in the gas pressure applied to the first surface of the hollow fiber membrane 3. Alternatively, the gas diffusion flow rate of the hollow fiber membrane 3 is measured, for example, based on fluctuations in the gas pressure in the space in contact with the second surface of the hollow fiber membrane 3. Alternatively, the gas diffusion flow rate of the hollow fiber membrane 3 is measured, for example, based on the amount of gas used to maintain a constant gas pressure applied to the first surface of the hollow fiber membrane 3. The pressure applied to the first surface of the hollow fiber membrane 3 is, for example, 5 kPa or more and 343 kPa or less, 34.5 kPa or more and 343 kPa or less, or 98 kPa or more and 345 kPa or less.

[0051] Examples of devices for measuring the gas diffusion flow rate of the hollow fiber membrane 3 include, but are not limited to, the Sartocheck® 5 Plus filter tester (SARTORIUS), Sartocheck 4 Plus filter tester (SARTORIUS), Palltronic® Flowstar V filter integrity tester (PALL), Palltronic Flowstar IV filter integrity tester (PALL), and Integritest® 5 (Merck).

[0052] The integrity test according to this embodiment will be further explained using the flowchart shown in Figure 4. In step S101, the membrane module 1 is positioned so that its longitudinal direction is parallel to the direction of gravity, with the first header 5A on the upper side in the direction of gravity and the second header 5B on the lower side in the direction of gravity. The opening 51A of the first header 5A and the opening 51B of the second header 5B are opened. The ports 21A and 21B of the cylindrical container 2 are also closed.

[0053] In step S102, liquid is introduced into the membrane module 1 through the opening 51B of the second header 5B. The liquid is, for example, water, but is not particularly limited. The liquid enters the space in contact with the first surface of each of the multiple hollow fiber membranes 3 via the space 50B in the second header 5B, and the space in contact with the first surface of each of the multiple hollow fiber membranes 3, and the space of the first header 5A are filled with liquid. After that, the opening 51A of the first header 5A is closed and the port 21A is opened, so that in each of the multiple hollow fiber membranes 3, the liquid passes from the first surface to the second surface, wetting each of the multiple hollow fiber membranes 3, and the space 20 in contact with the second surface of the hollow fiber membranes 3 in the cylindrical container 2 is filled with liquid. After the spaces in contact with the first surfaces of each of the multiple hollow fiber membranes 3 and the space 20 in contact with the second surface of the hollow fiber membranes 3 inside the cylindrical container 2 are filled with liquid, the port 21A of the cylindrical container 2 may be closed.

[0054] Alternatively, the space 20 in contact with the second surface of the hollow fiber membrane 3 inside the cylindrical container 2 may be filled with liquid first. In this case, the liquid passes from the second surface to the first surface in each of the multiple hollow fiber membranes 3, wetting each of the multiple hollow fiber membranes 3, and filling the space in contact with the first surface of each of the multiple hollow fiber membranes 3 with liquid.

[0055] In step S103, while the space 20 in contact with the second surface of the hollow fiber membrane 3 inside the cylindrical container 2 is filled with liquid, the liquid is removed from the space in contact with the first surface of the hollow fiber membrane 3. For example, with the opening 51A of the first header 5A open, the opening 51B of the second header 5B is opened, and the liquid is allowed to fall out of the opening 51B of the second header 5B due to gravity. Next, optionally, while the space 20 in contact with the second surface of the hollow fiber membrane 3 inside the cylindrical container 2 is filled with liquid, the liquid remaining on the first surface of the hollow fiber membrane 3 is removed by flowing gas (air blow treatment) from the opening 51A of the first header 5A into the space in contact with the first surface of the hollow fiber membrane 3. The gas that flows through the space in contact with the first surface of the hollow fiber membrane 3 and the liquid that has separated from the first surface of the hollow fiber membrane 3 are discharged from the opening 51B of the second header 5B. Flowing gas through the space in contact with the first surface of the hollow fiber membrane 3 is optional.

[0056] In step S104, for example, the ports 21A and 21B of the cylindrical container 2 are opened, and the liquid filling the space 20 in contact with the second surface of the hollow fiber membrane 3 inside the cylindrical container 2 is removed by suction from port 21B. The second surface of the hollow fiber membrane 3 is left wet. It is not necessary to remove the liquid remaining on the second surface of the hollow fiber membrane 3. Alternatively, after removing the liquid from the second surface in step S104, pre-pressurization (second pressurization) may be performed before performing the air diffusion flow rate measurement in step S105, which will be described later. Pre-pressurization refers to pressurizing the first surface of the hollow fiber membrane with gas before the air diffusion flow rate measurement in step S105. By extending the pressurization history, the liquid in the space in contact with the first surface of the hollow fiber membrane 3 before the air diffusion flow rate measurement can be sufficiently removed even if the air blow treatment is omitted, and / or the membrane is stabilized. More specifically, pre-pressurization is the operation of pressurizing the first surface of the porous membrane with gas after the liquid filling the spaces in contact with the first surface and the spaces in contact with the second surface has been removed and before pressurization for measuring the gas diffusion flow rate of the porous membrane. The pressure for pre-pressurization can be set arbitrarily, but it may be the same pressure as when measuring the air diffusion flow rate in step S105, for example. Pre-pressurization may also be performed in multiple stages. For example, after performing the first stage of pre-pressurization, the pressurized pressure may be set to 0, and then the second stage of pre-pressurization may be performed. The pressurization time per pre-pressurization can be set arbitrarily, but it may be, for example, 1 minute or more and 30 minutes or less. Note that when pre-pressurization is performed, the air blow treatment may be omitted.

[0057] In step S105, the first surface of the moistened hollow fiber membrane is pressurized with gas, and the gas diffusion flow rate of the hollow fiber membrane is measured. The gas diffusion flow rate of the hollow fiber membrane may be measured while the second surface of the hollow fiber membrane is covered with a liquid film. The gas diffusion flow rate of the hollow fiber membrane may be measured within 24 hours, within 20 hours, or within 16 hours after removing the liquid filling the space in contact with the second surface of the hollow fiber membrane in the membrane module 1. Measuring the gas diffusion flow rate of the hollow fiber membrane within 24 hours tends to maintain the moist state of the hollow fiber membrane.

[0058] In Figure 4, after removing the liquid from the space in contact with the first surface of the hollow fiber membrane 3 in step S103, the liquid filling the space 20 in contact with the second surface of the hollow fiber membrane 3 inside the cylindrical container 2 is removed in step S104. This embodiment is not limited to this, and the liquid filling the space 20 in contact with the second surface of the hollow fiber membrane 3 inside the cylindrical container 2 may be removed first, and then the liquid may be removed from the space in contact with the first surface of the hollow fiber membrane 3. In this case, the second surface and interior of the hollow fiber membrane 3 should not dry out, but should remain moist.

[0059] In the above, we have described an example in which the porous membrane is a porous hollow fiber membrane, where the inner circumferential surface of the hollow fiber membrane is the first surface and the outer circumferential surface is the second surface. However, when the porous membrane is a porous hollow fiber membrane, the outer circumferential surface of the hollow fiber membrane may be the first surface and the inner circumferential surface may be the second surface.

[0060] Conventionally, it has been considered difficult to measure the gas diffusion flow rate of a membrane when the membrane area is small. Furthermore, even if the membrane area is large, it has been considered difficult to measure the gas diffusion flow rate of a membrane when the pressure applied to the first surface of the membrane is low. Conventionally, when measuring the gas diffusion flow rate of a membrane, liquid is filled into the space in contact with the second surface of the hollow fiber membrane within the membrane module. In contrast, the inventors of the present invention have found that when measuring the gas diffusion flow rate of a hollow fiber membrane, by removing the liquid from the space in contact with the second surface of the hollow fiber membrane while maintaining the moisture of the hollow fiber membrane within the hollow fiber membrane module, it is possible to measure the gas diffusion flow rate of the hollow fiber membrane even when the membrane area of ​​the hollow fiber membrane within the module is small, and it is also possible to measure the gas diffusion flow rate of the hollow fiber membrane even when the pressure applied to the first surface of the hollow fiber membrane is low.

[0061] According to the integrity test method for a membrane module containing a hollow fiber membrane of this embodiment, it is possible to accurately measure the gas diffusion flow rate of the hollow fiber membrane even if the area of ​​the hollow fiber membrane is small. Furthermore, according to the integrity test method for a membrane module containing a hollow fiber membrane of this embodiment, it is possible to accurately measure the gas diffusion flow rate of the hollow fiber membrane even if the pressure applied to the first surface of the hollow fiber membrane is low.

[0062] The present invention will be described in more detail below with reference to examples. However, the present invention is not limited to the following examples and can be implemented in any form without departing from the spirit of the invention.

[0063] (Example 1) Hollow fiber membrane with a surface area of ​​0.03 m ２ A hollow fiber membrane module (Planova® FG1, Asahi Kasei Medical) was prepared. The hollow fiber membrane module was arranged so that its longitudinal direction was parallel to the direction of gravity. A Paltronic® Flowstar IV filter integrity tester (PALL) was also prepared. The detection limit of the Flowstar IV filter integrity tester is 0.1 mL / min. The space in contact with the inner surface of the hollow fiber membrane was filled with water, and the water was allowed to permeate the hollow fiber membrane, filling the space in contact with the outer surface of the hollow fiber membrane inside the cylindrical container of the module with water.

[0064] While the space in contact with the outer surface of the hollow fiber membrane was filled with water, the water in the space in contact with the inner surface of the hollow fiber membrane was discharged outside the hollow fiber membrane module by gravity. Furthermore, while the space in contact with the outer surface of the hollow fiber membrane was still filled with water, air was flowed into the space in contact with the inner surface of the hollow fiber membrane to remove any remaining water on the inner surface of the hollow fiber membrane. After that, the water in the space in contact with the outer surface of the hollow fiber membrane was discharged outside the hollow fiber membrane module.

[0065] Immediately after draining the water filling the space in contact with the outer surface of the hollow fiber membrane, a pressure of 343 kPa was applied to the space in contact with the inner surface of the hollow fiber membrane, and the air diffusion flow rate (ADR) was measured for 27 minutes using a Flowstar IV filter integrity tester. No errors occurred during the measurement. The average value of the measured air diffusion flow rate was 0.52 mL / min, the standard deviation was 0.05, and the coefficient of variation was 0.10. The pinhole diameter of the hollow fiber membrane estimated from the air diffusion flow rate was 3.37 μm, and the parvovirus removal rate (PPV-LRV) was 5.21. The results are shown in Figures 5 and 6.

[0066] (Example 2) The air diffusion flow rate was measured in the same manner as in Example 1, except that the air diffusion flow rate was measured 2 hours after the water filling the space in contact with the outer surface of the hollow fiber membrane was drained. No errors occurred during the measurement. The average value of the measured air diffusion flow rate was 0.45 mL / min. The results are shown in Figures 5 and 6.

[0067] (Example 3) The air diffusion flow rate was measured in the same manner as in Example 1, except that the air diffusion flow rate was measured 24 hours after the water filling the space in contact with the outer surface of the hollow fiber membrane was drained. No errors occurred during the measurement. The average value of the measured air diffusion flow rate was 0.65 mL / min. The results are shown in Figures 5 and 6.

[0068] (Example 4) Hollow fiber membrane with a surface area of ​​0.1 m ２ Using a hollow fiber membrane module (Planova® FG1, Asahi Kasei Medical), the air diffusion flow rate was measured in the same manner as in Example 1, except that the measurement time was 7 minutes. No errors occurred during the measurement. The average value of the measured air diffusion flow rate was 1.54 mL / min, the standard deviation was 0.20, and the coefficient of variation was 0.13. The pinhole diameter of the hollow fiber membrane estimated from the air diffusion flow rate was 6.28 μm, and the parvovirus removal rate (PPV-LRV) was 4.85. The results are shown in Figures 5 and 6.

[0069] (Example 5) Hollow fiber membrane with a surface area of ​​0.1 m ２ A hollow fiber membrane module (Planova® FG1, Asahi Kasei Medical) was prepared, and the space in contact with the inner surface of the hollow fiber membrane was filled with water in the same manner as in Example 1, allowing the water to permeate the hollow fiber membrane, and the space in contact with the outer surface of the hollow fiber membrane inside the cylindrical container of the module was filled with water. The water that filled the space in contact with the outer surface of the hollow fiber membrane was discharged outside the hollow fiber membrane module. Subsequently, the water that filled the space in contact with the inner surface of the hollow fiber membrane was discharged outside the hollow fiber membrane module by gravity. No air was flowed into the space in contact with the inner surface of the hollow fiber membrane.

[0070] Immediately after draining the water filling the space in contact with the inner surface of the hollow fiber membrane, a pressure of 343 kPa was applied to the space in contact with the inner surface of the hollow fiber membrane, and the air diffusion flow rate was measured for 27 minutes using a Flowstar IV filter integrity test apparatus. No errors occurred during the measurement. The average value of the measured air diffusion flow rate was 1.79 mL / min, the standard deviation was 0.18, and the coefficient of variation was 0.10. The results are shown in Figures 5 and 6.

[0071] (Example 6) Hollow fiber membrane with a surface area of ​​0.3 m ２ A hollow fiber membrane module (Planova® 35N, Asahi Kasei Medical) was prepared. The hollow fiber membrane modules were arranged so that their longitudinal direction was parallel to the direction of gravity. A Paltronic® Flowstar IV filter integrity test apparatus (PALL) was also prepared. The space in contact with the inner surface of the hollow fiber membrane was filled with water, and water was allowed to permeate the hollow fiber membrane, filling the space in contact with the outer surface of the hollow fiber membrane inside the cylindrical container of the module with water.

[0072] The space in contact with the outer surface of the hollow fiber membrane was filled with water, while the water in the space in contact with the inner surface of the hollow fiber membrane was discharged outside the hollow fiber membrane module by gravity. No air was introduced into the space in contact with the inner surface of the hollow fiber membrane. Subsequently, the water in the space in contact with the outer surface of the hollow fiber membrane was discharged outside the hollow fiber membrane module.

[0073] Immediately after draining the water filling the space in contact with the outer surface of the hollow fiber membrane, a pressure of 98 kPa was applied to the space in contact with the inner surface of the hollow fiber membrane, and the air diffusion flow rate was measured for 30 minutes using a Flowstar IV filter integrity test apparatus. No errors occurred during the measurement. The average value of the measured air diffusion flow rate was 1.80 mL / min, the standard deviation was 0.10, and the coefficient of variation was 0.05. The results are shown in Figures 5 and 6.

[0074] (Example 7) Hollow fiber membrane with a surface area of ​​1.0 m ２A hollow fiber membrane module (Planova® BioEX, Asahi Kasei Medical) was prepared. The hollow fiber membrane module was arranged so that its longitudinal direction was parallel to the direction of gravity. In addition, Integrite® 5 (Merck) was prepared. The detection limit of Integrite® 5 is 0.5 mL / min. The space in contact with the inner surface of the hollow fiber membrane was filled with water, and water was allowed to permeate the hollow fiber membrane, filling the space in contact with the outer surface of the hollow fiber membrane inside the cylindrical container of the module with water.

[0075] The space in contact with the outer surface of the hollow fiber membrane was filled with water, while the water in the space in contact with the inner surface of the hollow fiber membrane was discharged outside the hollow fiber membrane module by gravity. No air was introduced into the space in contact with the inner surface of the hollow fiber membrane. Subsequently, the water in the space in contact with the outer surface of the hollow fiber membrane was discharged outside the hollow fiber membrane module.

[0076] Immediately after draining the water filling the space in contact with the outer surface of the hollow fiber membrane, a pressure of 35 kPa was applied to the space in contact with the inner surface of the hollow fiber membrane, and the air diffusion flow rate was measured using Integritest® 5. The measurement time was automatically set by the device. No errors occurred during the measurement. The average value of the measured air diffusion flow rate was 0.78 mL / min. The results are shown in Figures 5 and 6.

[0077] (Comparative Example 1) Hollow fiber membrane with a surface area of ​​0.03 m² ２ A hollow fiber membrane module (Planova® FG1, Asahi Kasei Medical) was prepared. The hollow fiber membrane modules were arranged so that their longitudinal direction was parallel to the direction of gravity. A Paltronic® Flowstar IV filter integrity test apparatus (PALL) was also prepared. The space in contact with the inner surface of the hollow fiber membrane was filled with water, and water was allowed to permeate the hollow fiber membrane, filling the space in contact with the outer surface of the hollow fiber membrane inside the cylindrical container of the module with water.

[0078] The space in contact with the outer surface of the hollow fiber membrane was filled with water, while the water in the space in contact with the inner surface of the hollow fiber membrane was discharged outside the hollow fiber membrane module by gravity. Furthermore, while the space in contact with the outer surface of the hollow fiber membrane remained filled with water, air was flowed into the space in contact with the inner surface of the hollow fiber membrane to remove any remaining water on the inner surface. After that, the water in the space in contact with the outer surface of the hollow fiber membrane was not discharged outside the hollow fiber membrane module.

[0079] With water filling the space in contact with the outer surface of the hollow fiber membrane, an atmospheric pressure of 343 kPa was applied to the space in contact with the inner surface of the hollow fiber membrane, and an attempt was made to measure the air diffusion flow rate using a Flowstar IV filter integrity test apparatus. However, an error occurred indicating that the air diffusion flow rate was below the detection limit, and the measurement could not be performed. The results are shown in Figures 7 and 8.

[0080] (Comparative Example 2) Hollow fiber membrane with a surface area of ​​0.03 m² ２ A hollow fiber membrane module (Planova® FG1, Asahi Kasei Medical) was prepared. The hollow fiber membrane modules were arranged so that their longitudinal direction was parallel to the direction of gravity. A Paltronic® Flowstar IV filter integrity test apparatus (PALL) was also prepared. The space in contact with the inner surface of the hollow fiber membrane was filled with water, and water was allowed to permeate the hollow fiber membrane, filling the space in contact with the outer surface of the hollow fiber membrane inside the cylindrical container of the module with water.

[0081] The water filling the space in contact with the outer surface of the hollow fiber membrane was discharged outside the hollow fiber membrane module. Subsequently, the port of the cylindrical container of the hollow fiber membrane module was closed, and the water filling the space in contact with the inner surface of the hollow fiber membrane was discharged outside the hollow fiber membrane module by gravity. Furthermore, air was flowed into the space in contact with the inner surface of the hollow fiber membrane to remove any remaining water on the inner surface of the hollow fiber membrane.

[0082] An attempt was made to measure the air diffusion flow rate using a Flowstar IV filter integrity test apparatus by applying a pressure of 343 kPa to the space in contact with the inner surface of the hollow fiber membrane, but an error occurred and the measurement could not be performed. This is thought to be because when the port of the cylindrical container of the hollow fiber membrane module is closed with no liquid in the space in contact with the outer surface of the hollow fiber membrane, and air is flowed into the space in contact with the inner surface of the hollow fiber membrane, the pressure in the space in contact with the outer surface of the hollow fiber membrane increases, causing the water remaining on the outer surface of the hollow fiber membrane to flow back to the inner surface side of the hollow fiber membrane and be discharged outside the hollow fiber membrane along with the airflow from the space in contact with the inner surface of the hollow fiber membrane, thus drying the hollow fiber membrane and preventing it from becoming wet. The results are shown in Figures 7 and 8.

[0083] (Comparative Example 3) Hollow fiber membrane with a surface area of ​​0.1 m ２ A hollow fiber membrane module (Planova® FG1, Asahi Kasei Medical) was prepared. The hollow fiber membrane modules were arranged so that their longitudinal direction was parallel to the direction of gravity. A Paltronic® Flowstar IV filter integrity test apparatus (PALL) was also prepared. The space in contact with the inner surface of the hollow fiber membrane was filled with water, and water was allowed to permeate the hollow fiber membrane, filling the space in contact with the outer surface of the hollow fiber membrane inside the cylindrical container of the module with water.

[0084] The space in contact with the outer surface of the hollow fiber membrane was filled with water, while the water in the space in contact with the inner surface of the hollow fiber membrane was discharged outside the hollow fiber membrane module by gravity. Furthermore, while the space in contact with the outer surface of the hollow fiber membrane remained filled with water, air was flowed into the space in contact with the inner surface of the hollow fiber membrane to remove any remaining water on the inner surface. After that, the water in the space in contact with the outer surface of the hollow fiber membrane was not discharged outside the hollow fiber membrane module.

[0085] With water filling the space in contact with the outer surface of the hollow fiber membrane, an atmospheric pressure of 343 kPa was applied to the space in contact with the inner surface of the hollow fiber membrane, and an attempt was made to measure the air diffusion flow rate using a Flowstar IV filter integrity test apparatus. However, an error occurred indicating that the air diffusion flow rate was below the detection limit, and the measurement could not be performed. The results are shown in Figures 7 and 8.

[0086] (Comparative Example 4) Hollow fiber membrane with a surface area of ​​0.3 m ２A hollow fiber membrane module (Planova® 35N, Asahi Kasei Medical) was prepared. The hollow fiber membrane modules were arranged so that their longitudinal direction was parallel to the direction of gravity. A Paltronic® Flowstar IV filter integrity test apparatus (PALL) was also prepared. The space in contact with the inner surface of the hollow fiber membrane was filled with water, and water was allowed to permeate the hollow fiber membrane, filling the space in contact with the outer surface of the hollow fiber membrane inside the cylindrical container of the module with water.

[0087] The space in contact with the outer surface of the hollow fiber membrane was filled with water, while the water in the space in contact with the inner surface of the hollow fiber membrane was discharged outside the hollow fiber membrane module by gravity. No air was introduced into the space in contact with the inner surface of the hollow fiber membrane. Subsequently, the water in the space in contact with the outer surface of the hollow fiber membrane was not discharged outside the hollow fiber membrane module.

[0088] With water filling the space in contact with the outer surface of the hollow fiber membrane, an air pressure of 98 kPa was applied to the space in contact with the inner surface of the hollow fiber membrane, and an attempt was made to measure the air diffusion flow rate using a Flowstar IV filter integrity test apparatus. However, an error occurred indicating that the air diffusion flow rate was below the detection limit, and the measurement could not be performed. The results are shown in Figures 7 and 8.

[0089] (Comparative Example 5) Hollow fiber membrane with a surface area of ​​1.0 m ２ A hollow fiber membrane module (Planova® BioEX, Asahi Kasei Medical) was prepared. The hollow fiber membrane modules were arranged so that their longitudinal direction was parallel to the direction of gravity. In addition, Integritest® 5 (Merck) was prepared. The space in contact with the inner surface of the hollow fiber membrane was filled with water, and water was allowed to permeate the hollow fiber membrane, filling the space in contact with the outer surface of the hollow fiber membrane inside the cylindrical container of the module with water.

[0090] The space in contact with the outer surface of the hollow fiber membrane was filled with water, while the water in the space in contact with the inner surface of the hollow fiber membrane was discharged outside the hollow fiber membrane module by gravity. No air was introduced into the space in contact with the inner surface of the hollow fiber membrane. Subsequently, the water in the space in contact with the outer surface of the hollow fiber membrane was not discharged outside the hollow fiber membrane module.

[0091] With water filling the space in contact with the outer surface of the hollow fiber membrane, an atmospheric pressure of 35 kPa was applied to the space in contact with the inner surface of the hollow fiber membrane, and an attempt was made to measure the air diffusion flow rate using Integritest® 5. However, an error occurred indicating that the air diffusion flow rate was below the detection limit, and the measurement could not be performed. The results are shown in Figures 7 and 8.

[0092] (Example 8) Hollow fiber membrane with a surface area of ​​0.1 m ２ A hollow fiber membrane module (Planova® FG1, Asahi Kasei Medical) was prepared, and the space in contact with the inner surface of the hollow fiber membrane was filled with water in the same manner as in Example 1, allowing the water to permeate the hollow fiber membrane, and the space in contact with the outer surface of the hollow fiber membrane inside the cylindrical container of the module was filled with water. The water that filled the space in contact with the outer surface of the hollow fiber membrane was discharged outside the hollow fiber membrane module. Subsequently, the water that filled the space in contact with the inner surface of the hollow fiber membrane was discharged outside the hollow fiber membrane module by gravity. No air was flowed into the space in contact with the inner surface of the hollow fiber membrane.

[0093] Immediately after draining the water filling the space in contact with the inner surface of the hollow fiber membrane, pre-pressurization was performed at 343 kPa for 3 minutes using Integritest® 5. Subsequently, an atmospheric pressure of 343 kPa was applied to the space in contact with the inner surface of the hollow fiber membrane, and the air diffusion flow rate was measured. The measurement time was automatically set by the device. No errors occurred during the measurement. The average value of the measured air diffusion flow rate was 1.41 mL / min, the standard deviation was 0.13, and the coefficient of variation was 0.09. The results are shown in Figures 5 and 6. The pinhole diameter of the hollow fiber membrane estimated from the air diffusion flow rate was 6.69 μm, and the parvovirus removal rate (PPV-LRV) was 4.76.

[0094] (Example 9) Hollow fiber membrane with a surface area of ​​0.1 m ２A hollow fiber membrane module (Planova® FG1, Asahi Kasei Medical) was prepared, and the space in contact with the inner surface of the hollow fiber membrane was filled with water in the same manner as in Example 1, allowing the water to permeate the hollow fiber membrane, and the space in contact with the outer surface of the hollow fiber membrane inside the cylindrical container of the module was filled with water. The water that filled the space in contact with the outer surface of the hollow fiber membrane was discharged outside the hollow fiber membrane module. Subsequently, the water that filled the space in contact with the inner surface of the hollow fiber membrane was discharged outside the hollow fiber membrane module by gravity. No air was flowed into the space in contact with the inner surface of the hollow fiber membrane.

[0095] Immediately after draining the water filling the space in contact with the inner surface of the hollow fiber membrane, the first pre-pressurization was performed using Integritest® 5 at 343 kPa for 30 minutes, followed by depressurization for 10 minutes, and then a second pre-pressurization at 343 kPa for 20 minutes. Subsequently, a pressure of 343 kPa was applied to the space in contact with the inner surface of the hollow fiber membrane, and the air diffusion flow rate was measured. The measurement time was automatically set by the device. No errors occurred during the measurement. The measured air diffusion flow rate was 1.59 mL / min. The results are shown in Figures 5 and 6.

[0096] (Comparative Example 6) Hollow fiber membrane with a surface area of ​​1.0 m ２ A hollow fiber membrane module (Planova® FG1, Asahi Kasei Medical) was prepared. The hollow fiber membrane modules were arranged so that their longitudinal direction was parallel to the direction of gravity. In addition, Integritest® 5 (Merck) was prepared. The space in contact with the inner surface of the hollow fiber membrane was filled with water, and the water was permeated through the hollow fiber membrane, filling the space in contact with the outer surface of the hollow fiber membrane inside the cylindrical container of the module with water.

[0097] The space in contact with the outer surface of the hollow fiber membrane was filled with water, while the water in the space in contact with the inner surface of the hollow fiber membrane was discharged outside the hollow fiber membrane module by gravity. No air was introduced into the space in contact with the inner surface of the hollow fiber membrane. Subsequently, the water in the space in contact with the outer surface of the hollow fiber membrane was not discharged outside the hollow fiber membrane module.

[0098] With water filling the space in contact with the outer surface of the hollow fiber membrane, pre-pressurization was performed for 3 minutes by applying a pressure of 343 kPa to the space in contact with the inner surface of the hollow fiber membrane using Integritest® 5. Subsequently, an attempt was made to measure the air diffusion flow rate, but an error occurred indicating that the air diffusion flow rate was below the detection limit, and the measurement could not be performed. The results are shown in Figures 7 and 8.

[0099] 1... Membrane module, 2... Cylindrical container, 3... Hollow fiber membrane, 4A... First retaining member, 4B... Second retaining member, 5A... First header, 5B... Second header, 20... Space, 21A, 21B... Port, 50A, 50B... Space, 51A, 51B... Opening

Claims

1. A method for testing the integrity of a membrane module containing a porous membrane having a first surface and a second surface opposite to the first surface, comprising: filling a space in the membrane module that is in contact with at least the second surface of the porous membrane with a liquid; removing the liquid that has been filled in the space in contact with the second surface of the porous membrane in the membrane module; and pressurizing the first surface of the wet porous membrane with a gas and measuring the gas diffusion flow rate of the porous membrane.

2. The method according to claim 1, wherein the liquid is filled into the space in contact with the first surface of the porous membrane, and the liquid is passed from the first surface to the second surface of the porous membrane to fill the space in contact with the second surface of the porous membrane in the membrane module with the liquid.

3. The method according to claim 2, further comprising removing the liquid from the space in contact with the first surface of the porous membrane while the space in contact with the second surface of the porous membrane in the membrane module remains filled with the liquid.

4. The method according to claim 3, wherein the liquid is dropped by gravity from the space in contact with the first surface of the porous membrane to the outside of the membrane module.

5. The method according to claim 3 or 4, further comprising filling the space in contact with the second surface of the porous membrane within the membrane module with the liquid, and flowing a gas through the space in contact with the first surface of the porous membrane.

6. The method according to claim 5, wherein the liquid is removed from the first surface of the porous membrane by flowing the gas into the space in contact with the first surface of the porous membrane.

7. The method according to claim 1, comprising: filling the space in contact with the first surface of the porous membrane with the liquid; removing the liquid filled in the space in contact with the first surface of the porous membrane; and pressurizing the first surface of the porous membrane with gas after the liquids filled in the space in contact with the first surface and the space in contact with the second surface have been removed and before pressurizing for measuring the gas diffusion flow rate of the porous membrane.

8. The method according to claim 1, wherein the gas diffusion flow rate of the porous membrane is measured based on fluctuations in the pressure applied to the first surface of the porous membrane.

9. The method according to claim 1, wherein the gas diffusion flow rate of the porous membrane is measured based on fluctuations in the pressure of the space in contact with the second surface of the porous membrane.

10. The method according to claim 1, wherein the gas diffusion flow rate of the porous membrane is measured based on the amount of gas used to maintain a constant pressure applied to the first surface of the porous membrane.

11. The method according to claim 1, wherein the porous membrane comprises at least one selected from regenerated cellulose, polyvinylidene fluoride, hydrophilic monomer, polystyrene polymer, and hydrophilic polymer.

12. The membrane area of ​​the porous membrane is 0.01 m². ２ 4.0m ２ The method according to claim 1, which is as follows.

13. The method according to claim 1, wherein the pressure applied to the first surface of the porous membrane is 34.5 kPa or more and 343 kPa or less.

14. The method according to claim 1, wherein the parvovirus removal rate (LRV) of the porous membrane is 4.0 or higher.

15. The method according to claim 1, wherein after removing the liquid filling the space in contact with the second surface of the porous membrane in the membrane module, the first surface of the porous membrane is pressurized with the gas while the second surface of the porous membrane is covered with a film of the liquid, and the gas diffusion flow rate of the porous membrane is measured.

16. The method according to claim 1, wherein, after removing the liquid filling the space in contact with the second surface of the porous membrane in the membrane module, the first surface of the porous membrane is pressurized with the gas and the gas diffusion flow rate of the porous membrane is measured within 24 hours.

17. The method according to claim 1, wherein the porous membrane is a porous hollow fiber membrane.

18. The method according to claim 17, wherein the inner circumferential surface of the porous hollow fiber membrane is the first surface, and the outer circumferential surface of the porous hollow fiber membrane is the second surface.

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