Hollow fiber membrane module, method for manufacturing the same, and cleaning method

Abstract

【Problem】 To maintain the filtration performance of a membrane while keeping it in a sterilized state. 【Solution】 In a hollow fiber membrane module 1, a bundle of hollow fiber membranes 3 is housed in a module housing 5. In the hollow fiber membrane module 1, both end portions of the bundle of hollow fiber membranes 3 are integrated with the module housing 5 by potting material. 90% or more of the porous portions of the bundle of hollow fiber membranes 3 contain a preservation liquid. The space portion inside the module housing 5 is filled with a gas in which no living bacteria exist and the preservation liquid.

Description

[Technical Field]

[0001] This invention relates to a hollow fiber membrane module and its manufacturing method. The hollow fiber membrane module is suitable for use in the filtration process of culture medium or fermentation broth as a filter for removing turbidity components from water to be treated, for the concentration and purification of target substances, or for the production of ultrapure water. [Background Technology]

[0002] In the use of hollow fiber membranes in the manufacturing processes of peptide drugs, protein drugs, and antibody drugs using E. coli, yeast, and animal cells, batch culture methods that remove unwanted components from the culture medium by filtration after cultivation and continuous culture methods that recover the target substance at any time during cultivation are suitable. These products require pre-sterilization to provide users with a state where only minimal cleaning is required for immediate use.

[0003] In order to maintain filtration performance while inhibiting the growth of microorganisms in the product during storage, aqueous solutions of glycerol, alcohol, or sodium hypochlorite have been used in conventional hollow fiber membrane modules. However, in recent years, there have also been examples of membrane modules filled with sterilized water to reduce the drainage of these storage solutions (for example, see Patent Documents 1 and 2). [Existing Technical Documents] [Patent Documents]

[0004] [Patent Document 1] Japanese Patent Application Publication No. 2018-089614 [Patent Document 2] International Publication No. 2015 / 099015 [Summary of the Invention] [The problem this invention aims to solve]

[0005] In Patent Document 1, since the interior of the membrane module is filled with pure water, a mechanism is needed to mitigate the pressure rise generated during the heating process. In Patent Document 2, since the membrane module is also filled with water, in addition to a mechanism to prevent pressure rise during the heating process, an isolation member is also required to prevent the expanding water from directly contacting the connected sterile connection components.

[0006] The purpose of this invention is to solve the above problems and provide a hollow fiber membrane module and its manufacturing method that can maintain filtration performance while preventing the hollow fiber membrane from drying out, and can maintain the sterility of the inside of the hollow fiber membrane module for a long time. [Methods used to solve problems]

[0007] To meet the aforementioned requirements, the inventors conducted repeated and in-depth research and verification. As a result, it was confirmed that sealing sterilized water and gas in a certain proportion inside the hollow fiber membrane module could satisfy all the requirements, thus leading to the invention. The invention is as follows.

[0008] [1] A hollow fiber membrane module, characterized in that a hollow fiber membrane bundle composed of multiple hollow fiber membranes is housed in the module housing. In a hollow fiber membrane module where both ends of the hollow fiber membrane bundle are integrated with the module housing via a potting material, 90% or more of the porous portion of the hollow fiber membrane bundle contains water, i.e., a preservation solution, that does not contain viable bacteria. The space inside the component housing is filled with gas and the preservation liquid, which contain no living bacteria. [2] The hollow fiber membrane module according to [1] is characterized in that, when the opening for piping connection present on the module housing is sealed by a sealing member... Let the volume of the first space surrounded by the inner surface of the cover installed on the component housing, the end face of the potting material, and the inner surface and end faces of the hollow fiber membrane be defined as Vfirst. Let the volume of the second space surrounded by the inner surface of the component housing, the end face of the potting material, and the outer surface of the hollow fiber membrane be defined as Vsecond. The volume of the third space formed by the porous portion of the hollow fiber membrane is defined as V_pore. Let the total volume of Vfirst, Vsecond, and Vhole be Vtotal. Let the volume of the preservation fluid existing in the first space be W_first. Let the volume of the preservation liquid existing in the second space be W_second. Let the total volume of the preservation fluid present in the third space be W_hole. When the total volume of W_first, W_second, and W_hole is set as W_total, the following equation (1) is satisfied. 0.35≦W_total / V_total≦0.95···(1) [3] The hollow fiber membrane module according to [1] or [2] is characterized in that the ratio of W first to V first is less than or equal to the ratio of W second to V second. [4] The hollow fiber membrane module according to any one of [1] to [3] is characterized in that the ratio of W second to V second is greater than or equal to 0.8 and less than or equal to 1. [5] The hollow fiber membrane assembly according to any one of [1] to [4] is characterized in that it comprises: a pair of fixing portions at both ends of the hollow fiber membrane bundle within the assembly housing, formed by a potting material sealing the gaps between the outer surfaces of the hollow fiber membranes and between the outer surfaces and the inner surface of the cylindrical housing; and a pair of rectifier tubes located at the center side of the assembly housing along the length direction of the pair of fixing portions, respectively surrounding both ends of the hollow fiber membrane bundle, wherein... In the rectifier cylinder, the separation width between the end located on the fixed part side and the fixed part is 1 mm or more and 20 mm or less. [6] The hollow fiber membrane module according to any one of [1] to [5] is characterized in that the TOC of the preservation liquid contained in the module housing is 1 ppm or more and less than 50 ppm. [7] The hollow fiber membrane module according to any one of [1] to [6] is characterized in that all openings for piping connections provided in the module housing are sealed by blind flanges. The linear expansion coefficient of the raw material used in the blind flange is between 0.95 and 1.05 times that of the component housing. [8] The hollow fiber membrane assembly according to [1] is characterized in that it is packaged by a packaging film having at least a portion of a first portion that is gas permeable. [9] The hollow fiber membrane module according to [8] is characterized in that the module housing is cylindrical, and at least a portion of the opening for piping connection provided in the module housing protrudes in a direction orthogonal to the length direction of the module housing. The second portion, which is packaged by the packaging film such that the gas permeability of the packaging film is lower than that of the first portion, is located within a range of 120° centered on the direction of rotation of the protruding direction of the opening in the circumferential direction of the component housing, or within a range of 60° centered on the opposite direction of the protruding direction.

[10] The hollow fiber membrane module according to any one of [1] to [9] is characterized in that a sterile connector is installed at the piping connection opening provided in the module housing. The sterile connector includes a sterilization filter. One end face of the sterilization filter is in direct contact with the space inside the hollow fiber membrane module.

[11] A method for manufacturing a hollow fiber membrane module, characterized in that a hollow fiber membrane bundle consisting of multiple hollow fiber membranes is inserted into the module housing. In a hollow fiber membrane module where both ends of the hollow fiber membrane bundle are integrally formed with the module housing by a potting material, 90% or more of the porous portion of the hollow fiber membrane bundle is filled with water (a preservation solution) devoid of viable bacteria, and the space within the module housing is filled with gas (also devoid of viable bacteria) and the preservation solution. When the piping connections on the component housing are sealed by a blind flange, the volume of the first space surrounded by the inner surface of the cover installed on the component housing, the end face of the potting material, and the inner surface and end faces of the hollow fiber membrane is defined as Vfirst; the volume of the second space surrounded by the inner surface of the pipe portion of the component housing, the end face of the potting material, and the outer surface of the hollow fiber membrane is defined as Vsecond; the volume of the third space formed by the porous portion of the hollow fiber membrane is defined as Vhole; the total volume of Vfirst, Vsecond, and Vhole is defined as Vtotal; the volume of water in the first space is defined as Wfirst; the volume of water in the second space is defined as Wsecond; the total volume of water in the third space is defined as Whole; and the total volume of Wfirst, Wsecond, and Whole is defined as Wtotal. Therefore, the total volume inside the hollow fiber membrane module is adjusted to a relationship of 0.35 ≤ Wtotal / Vtotal ≤ 0.95. Furthermore, with the opening for pipe connection sealed, the water and gas in the hollow fiber membrane module are transformed into a state free of live bacteria by heat treatment at 80°C or higher and 125°C or lower.

[12] The method for manufacturing a hollow fiber membrane module according to

[11] is characterized in that, in the process of heating the hollow fiber membrane module containing the pure water and the gas, the relative humidity inside the module housing is maintained at 85% or higher.

[13] The method for manufacturing a hollow fiber membrane module according to

[11] or

[12] is characterized in that, in the process of heating the module housing containing the water and the gas, the exterior of the hollow fiber membrane module is heated by dry air.

[14] The method for manufacturing a hollow fiber membrane module according to any one of

[11] to

[13] is characterized in that, in the hollow fiber membrane module in which a sterile connector is installed at the opening for piping connection provided in the module housing, the pressure difference between the inside of the module housing and the outside of the module housing at 20°C before the start of the heat treatment is 0 kPa, and the pressure difference between the inside of the module housing and the outside of the module housing separated by the sterilization filter of the sterile connector during the heat treatment is 20 kPa or less.

[15] The method for manufacturing a hollow fiber membrane module according to any one of

[11] to

[14] is characterized in that, in the step of heating the module housing containing the water and the gas, Heating is performed with the piping connection openings in the component housing sealed by a blind flange.

[16] A method for manufacturing a hollow fiber membrane module according to any one of

[11] to

[15] , characterized in that the hollow fiber membrane module is heat-treated while being packaged in a packaging film having at least a portion of a first portion that is gas permeable.

[17] The method for manufacturing a hollow fiber membrane module according to

[16] is characterized in that the module housing is cylindrical, and at least a portion of the opening for piping connection provided in the module housing protrudes in a direction orthogonal to the length direction of the module housing. In the process of heating the hollow fiber membrane assembly containing the water and the gas, a second portion, packaged by the packaging film such that the gas permeability of the packaging film is lower than that of the first portion, is located within a range of 120° centered on the direction of rotation of 90° from the protruding direction of the opening, or within a range of 60° centered on the opposite direction of the protruding direction, in the circumferential direction of the axis of the assembly housing.

[18] A method for cleaning a hollow fiber membrane module, characterized in that, when cleaning the interior of the hollow fiber membrane module manufactured by any one of the manufacturing methods in

[11] to

[17] using filtration cleaning, By measuring the unit membrane area of ​​the hollow fiber membrane at 20 L / m² 2 Filter pure water of 500 ppb or less to achieve a TOC of 500 ppb or less. [Invention Effects]

[0009] According to the filter membrane assembly of the present invention, since it contains water and gas free of viable bacteria as a preservation liquid for maintaining the filtration performance of the filter membrane assembly in an appropriate proportion, it is possible to provide a hollow fiber membrane assembly that is sterilized while maintaining the filtration performance of the membrane.

[0010] As a pretreatment of the hollow fiber membrane module before use, gamma ray sterilization or electron beam irradiation sterilization can be appropriately selected. However, even under such circumstances, the environment inside the hollow fiber membrane module can be maintained in a certain state before irradiation. Therefore, it is not necessary to adjust the irradiation amount each time, and sterilization can be achieved with minimal irradiation.

[0011] Furthermore, once the filter assembly of the present invention is installed on the device, it can begin filtration operation after minimal rinsing. [Attached Image Description]

[0012] Figure 1 This is a cross-sectional view showing the configuration of a hollow fiber membrane assembly using one embodiment of the filter membrane assembly of the present invention. Figure 2 This is an exploded perspective view of a hollow fiber membrane module. Figure 3 It is a cross-sectional view used to illustrate a portion of the interior space of a hollow fiber membrane module. Figure 4 It is a cross-sectional view used to illustrate other parts of the space inside the hollow fiber membrane module. Figure 5 It is a cross-sectional view used to illustrate the interior space of a hollow fiber membrane module and other parts of the space. Figure 6 This is a cross-sectional view showing the state in which the opening for piping connection of the hollow fiber membrane module is sealed with a blind flange. Figure 7 This is a cross-sectional view showing the state of the piping connection opening of the hollow fiber membrane module sealed with a sterile connector. Figure 8 This is a diagram used to show the location of the second part in the packaging film that houses the hollow fiber membrane assembly. Figure 9 This is a diagram used to show other locations of the second part in the packaging film that houses the hollow fiber membrane assembly. Figure 10 It shows that it was used Figure 1 A diagram showing the detailed configuration of each part of the filtration device of the hollow fiber membrane module.

Detailed Implementation Methods

[0013] Hereinafter, a hollow fiber membrane module using an embodiment of the hollow fiber membrane module of the present invention will be described with reference to the accompanying drawings.

[0014] The hollow fiber membrane module of this embodiment can be used for cell separation after culture in biopharmaceutical manufacturing, as well as for the purification and concentration of biopharmaceuticals. The hollow fiber membrane module of this embodiment can also be used for internal pressure filtration. For hollow fiber membrane modules, high filtration performance is required to achieve equipment miniaturization; however, the hollow fiber membrane module of this embodiment can be used as a hollow fiber membrane module that can increase the filtration flow rate per unit volume.

[0015] Figure 1 This is a cross-sectional view showing a simplified configuration of the hollow fiber membrane module 1 according to this embodiment. Additionally, Figure 2 It is Figure 1 The diagram shows a three-dimensional view of the hollow fiber membrane module 1 as an exploded form.

[0016] like Figure 1 As shown, the hollow fiber membrane module 1 of this embodiment includes: a hollow fiber membrane bundle 3 formed by bundling multiple hollow fiber membranes 3a; and a cylindrical module housing (hereinafter sometimes referred to as "housing") 5 that houses the hollow fiber membrane bundle 3.

[0017] At the two end openings of the housing 5, there are pipe connection caps 10 and 11, forming pipes 10a and 11a for connecting to piping. The pipe connection caps 10 and 11 are fixedly installed on the housing 5 by nuts 13. The nuts 13 are screwed into the external threads formed on the sides of the two ends of the housing 5. By tightening the nuts 13, the two ends of the housing 5 are sealed with O-rings 12 disposed in the grooves of the caps 10 and 11.

[0018] In addition, an upper nozzle 5a and a lower nozzle 5b through which fluid flows are formed at both ends of the housing 5. The upper nozzle 5a and the lower nozzle 5b are configured to protrude in a direction orthogonal to the length direction of the housing 5.

[0019] At both ends of the hollow fiber membrane bundle 3, each hollow fiber membrane 3a has an opening. At these two ends, the hollow fiber membranes 3a are bonded together by a potting material to form a fixing part 14. The two ends of the hollow fiber membrane bundle 3 are integrated by the potting material.

[0020] In internal pressure filtration, for example, liquid flows in from cover 11, flows into the hollow portion of the open hollow fiber membrane, and permeates from the inner surface of each hollow fiber membrane 3a between the fixing portions 14 at both ends. After passing through the outer surface of each hollow fiber membrane, the liquid flows out from, for example, the upper nozzle 5a. In external pressure filtration, for example, liquid flows in from the lower nozzle 5b, permeates from the outer surface of each hollow fiber membrane 3a between the fixing portions 14 at both ends, and after passing through the hollow portion of each hollow fiber membrane 3a, the liquid flows out from the pipes 10a and 11a of covers 10 and 11.

[0021] As a hollow fiber membrane 3a, microfiltration membranes, ultrafiltration membranes, etc. can be used. There are no particular limitations on the raw materials for hollow fiber membranes, and examples include polysulfone, polyethersulfone, polyacrylonitrile, polyimide, polyetherimide, polyamide, polyetherketone, polyetheretherketone, polyethylene, polypropylene, poly(4-methylpentene), ethylene-vinyl alcohol copolymer, cellulose, cellulose acetate, polyvinylidene fluoride, ethylene-tetrafluoroethylene copolymer, polytetrafluoroethylene, etc. In addition, composite raw materials of these can also be used.

[0022] The inner diameter of the hollow fiber membrane 3a is from 50 μm to 3000 μm, preferably from 500 μm to 2000 μm. Since a smaller inner diameter leads to greater pressure loss, which negatively impacts filtration, an inner diameter of 50 μm or more is preferred for the hollow fiber membrane 3a. Furthermore, in configurations with larger inner diameters, maintaining the membrane shape during spinning is difficult; therefore, an inner diameter of 3000 μm or less is preferred.

[0023] As potting materials, epoxy resin, vinyl ester resin, polyurethane resin, unsaturated polyester resin, olefin polymers, silicone resin, fluorinated resin and other polymer materials are preferred. Any one of these polymer materials can be used, or a combination of multiple polymer materials can be used.

[0024] It should be noted that in the manufacturing processes of biopharmaceuticals and the production of ultrapure water for semiconductor applications, the constituent components are required to have heat resistance to hot water and low leaching during cleaning. Therefore, as the raw material for the hollow fiber membrane 3a, it is desirable to use raw materials with low leaching, such as polyvinylidene fluoride, polysulfone, polyethersulfone, or polyphenylsulfone. Similarly, as the raw material for the shell 5, raw materials with low leaching, such as polysulfone, are preferred. Furthermore, for the same reason, epoxy resin is preferably used as the potting material.

[0025] In addition, in the hollow fiber membrane module 1 of this embodiment, an appropriate amount of water devoid of viable bacteria is sealed in relative to the internal space of the shell as a preservation solution. Specifically, 90% or more of the porous portion of the hollow fiber membrane bundle 3 in the hollow fiber membrane module 1 contains the preservation solution. The preservation solution refers to the liquid used to maintain the filtration performance of the hollow fiber membrane 3a. The water devoid of viable bacteria is water sampled from the hollow fiber membrane module and cultured using a Total Count Sampler provided by Merck Millipore Corporation at 25°C to 35°C for 48 to 72 hours, and confirmed by visual inspection and a microscope with a magnification of approximately 20x to confirm the absence of bacterial colonies. The internal space, except for that occupied by the preservation solution, is occupied by gas devoid of viable bacteria. Therefore, with the hollow fiber membrane module sealed with a blind flange, the module was inverted 10 times along its length. Water samples were then incubated at 25°C to 35°C for 48 to 72 hours using total colony counting strips provided by Merck Millipore Corporation. Water and gas without colony formation were confirmed visually and under a microscope with approximately 20x magnification to be free of viable bacteria. The contained gas was preferably a gas that had undergone pre-particle removal via a HEPA filter or similar means. Air or a nitrogen atmosphere could be used to further suppress oxidative degradation of the components used in the hollow fiber membrane module during heat sterilization. Alternatively, the water and gas could be sterilized by heating after filling with the preservation solution and gas.

[0026] The space inside the hollow fiber membrane module is described here. With the openings for piping connections sealed by the sealing member, the space inside the hollow fiber membrane module 1 is divided into the following three areas. The openings for piping connections are specifically the upper nozzle 5a, the lower nozzle 5b, and pipes 10a and 11a. The sealing member is specifically the blind plate described later. Figure 3 As shown, the first space sp1, which is the first region, is defined by the inner surface of cover 10, the inner surface of cover 11, the first blind plate YY respectively mounted on covers 10 and 11, the end face of the opening side of the hollow fiber membrane 3a formed by the fixing part 14 and the hollow fiber membrane 3a, and the inner surface of the hollow fiber membrane 3a. The volume of the first space sp1 is defined as Vfirst. The first blind plate YY is a virtual flat plate that blocks the end faces of pipes 10a and 11a. Figure 4 As shown, the second space sp2, which is the second region, is defined by the inner surface of the housing 5, the end face of the fixing part 14 opposite to the opening side of the hollow fiber membrane 3a, the second blind plate ZZ respectively installed on the upper nozzle 5a and the lower nozzle 5b, and the outer surface of the hollow fiber membrane 3a. The volume of the second space is defined as Vsecond. The second blind plate ZZ is a virtual flat plate that blocks the end faces of the nozzle parts 5a and 5b. Figure 5 As shown, the third space sp3, which is the third region, is the space formed by the porous portion of the hollow fiber membrane 3a. The volume occupied by the third space sp3 is defined as V_pore. The total volume of V_first, V_second, and V_pore is defined as V_total. Furthermore, the volume of the preservation liquid in the first space sp1 is defined as W_first, the volume of the preservation liquid in the second space sp2 is defined as W_second, and the volume of the preservation liquid in the third space sp3 is defined as W_pore. The total volume of the preservation liquid in the first space sp1, the second space sp2, and the third space sp3 is defined as W_total.

[0027] Here, the preferred Wtotal / Vtotal ratio is 0.35 or higher and 0.95 or lower. When the ratio is less than 0.35, the preservative solution contained in the porous portion of the hollow fiber membrane 3a may evaporate during heat sterilization, potentially affecting its original filtration performance. Furthermore, when the ratio is less than 0.35, air bubbles may be generated during leak checks performed before filtration operation, which could be confused with leaks in the hollow fiber membrane. When the Wtotal / Vtotal ratio is greater than 0.95, the internal pressure of the housing 5 increases during heat sterilization, which may sometimes affect the product's durability.

[0028] Furthermore, when the water content of the porous portion of the hollow fiber membrane 3a is specified as W pores / V pores, the W pores / V pores ratio after heat sterilization is 0.9 or higher, preferably 0.98 or higher.

[0029] Furthermore, when the water content on the primary side of the hollow fiber membrane module is set to Wfirst / Vfirst and the water content on the secondary side is set to Wsecond / Vsecond, the preferred relationship between the water contents is Wfirst / Vfirst ≤ Wsecond / Vsecond. If Wfirst / Vfirst ≤ Wsecond / Vsecond, since the space Vsecond, which is preferentially heated during the heat sterilization process, contains a higher proportion of water, the process can be performed while suppressing the drying of the hollow fiber membrane. On the other hand, by making Wfirst / Vfirst smaller than Wsecond / Vsecond, the water that expands during the heat sterilization process moves from the outer surface side to the inner surface side through the porous portion of the hollow fiber membrane 3a, which can alleviate the rise in internal pressure of the housing 5. In addition, by reducing Wfirst / Vfirst, the hollow fiber membrane module 1 after filling with the preservation liquid can be made lighter, which is advantageous from the point of view of handling.

[0030] Furthermore, it is desirable that the moisture content Wsecond / Vsecond of the second space sp2 is 0.8 or higher and 1 or lower. If the moisture content Wsecond / Vsecond is 0.8 or higher, the temporary decrease in relative humidity of the second space sp2 during the heating process of the heat sterilization treatment can be suppressed, and the process time can be shortened. Furthermore, before the heat sterilization treatment, although it also depends on the filling rate of the hollow fiber membrane 3a relative to the inner diameter of the shell 5, if the moisture content Wsecond / Vsecond is 0.8 or higher, the outer surface can be completely immersed in water free of viable bacteria when the shell 5 is placed horizontally with its axial direction aligned, thus further reducing the occurrence of drying during heat sterilization. In addition, if the moisture content Wsecond / Vsecond is 0.8 or higher, the shaking of the hollow fiber membrane 3a caused by the shaking of air bubbles during the transport of the hollow fiber membrane assembly 1 can be suppressed, thereby reducing the possibility of breakage.

[0031] In the hollow fiber membrane assembly 1, rectifier cylinders 19a and 19b are disposed between the upper nozzle 5a and the lower nozzle 5b and the hollow fiber membrane 3a. The rectifier cylinders 19a and 19b can be cylinders coaxial with the inner circumference of the housing 5. One end of the rectifier cylinders 19a and 19b is preferably separated from the fixing part 14. The hollow fiber membrane assembly 1 used in biopharmaceutical manufacturing has a single-use method for disposal and a method for reuse after cleaning. In the reuse method, the hollow fiber membrane assembly 1 undergoes a thermal cycle for sterilization using hot water or steam at 80°C or higher. However, in a configuration where a portion of the rectifier cylinders 19a and 19b is embedded in the fixing part 14, this could become the starting point for cracks to form in the fixing part 14. On the other hand, as described above, by separating the rectifier cylinders 19a and 19b from the fixing part 14, it can be used in a healthy state for a longer period of time. Furthermore, the axial separation width of the housing 5, while varying depending on its position, is ideally between 1 mm and 20 mm. When the separation width is 1 mm or less, depending on the adhesive application method, the rectifier tubes 19a and 19b may come into contact with the fixing portion 14 in a certain area. Conversely, in configurations with a separation width of 20 mm or more, the filtrate or backwashing solution used during cleaning flows in from the separation area, increasing the local flow rate and potentially generating a load at the root of the hollow fiber membrane 3a, in other words, near the fixing portion 14.

[0032] Furthermore, in the hollow fiber membrane module 1 of this embodiment, the organic matter content in the storage solution is preferably 1 ppm or more and less than 50 ppm in terms of TOC (Total Organic Carbon). If the TOC is 1 ppm or more, the organic matter in the water will be preferentially oxidized during the water heating sterilization process described later, thus inhibiting the oxidative degradation of the hollow fiber membrane 3a caused by heating. It should be noted that the TOC is further preferably 5 ppm or more.

[0033] In addition, if the concentration is below 50 ppm, the concentration of organic matter in the storage solution at the start of use of the hollow fiber membrane module 1 can be rapidly reduced, and the time and amount of rinsing solution required for rinsing before operation can be reduced.

[0034] Furthermore, in the hollow fiber membrane module 1 of this embodiment, the concentration of metal ions in the preservation solution is preferably 10 ppb or more and less than 100 ppb. In biopharmaceutical processes, the introduction of metal ions that would adversely affect the produced drug should be avoided, and their content should be as low as possible. On the other hand, when considering sterilization, it is known that metal ions exhibit bactericidal effects. By including metal ions within a range that does not adversely affect drug manufacturing or within a range where rinsing can be easily performed, the sterilization effect of heating can be improved.

[0035] If the hollow fiber membrane module 1 of this embodiment is used, it can inhibit bacterial growth during storage while simultaneously providing filtration performance that meets the requirements for use in biomedicine. It should be noted that if the hollow fiber membrane module 1 of this embodiment is used, even as a final filter for ultrapure water production for semiconductor manufacturing applications, it can rapidly reduce the concentration of organic matter in the storage solution while still providing filtration performance.

[0036] like Figure 6 As shown, the upper nozzle 5a, lower nozzle 5b, and pipes 10a and 11a of the openings for piping connections preferably located in the housing 5 are all sealed by blind flanges 15, 16, 17, and 18, respectively. The material of the blind flanges 15, 16, 17, and 18 is preferably a material with a linear expansion coefficient that is 0.95 to 1.05 times that of the plastic raw material used in the housing 5. More preferably, it can be made of the same raw material as the components used in the housing 5. Furthermore, the blind flanges 15, 16, 17, and 18 may also have handles. For the hollow fiber membrane assembly 1 after heat sterilization, depending on the ambient temperature at the time of opening, the pressure inside the hollow fiber membrane assembly 1 may become negative compared to the outside, sometimes resulting in a tight seal. If handles are provided, the blind flanges 15, 16, 17, and 18 can be easily opened even in this situation. The shape of the handles can be appropriately selected from L-shaped, T-shaped, U-shaped, etc.

[0037] As a blind plate for the nozzle section of the sealing housing 5, such as Figure 7 As shown, a sterile connector 20 can also be used. A sterile connector 20 is a component that can be connected in a non-sterile environment without damaging the sterility of the internal structure of the connected piping, and is sometimes particularly suitable for single-use components. The sterile connector 20 may include a sterilization filter 21. One end face of the sterilization filter 20 may also be in direct contact with the internal space of the hollow fiber membrane assembly 1, in other words, with the first space sp1 and the second space sp2.

[0038] The hollow fiber membrane module 1 can be packaged in a plastic packaging film for storage and transportation to prevent moisture evaporation during storage. Low-density polyethylene, high-density polyethylene, polypropylene, and polyvinylidene chloride are preferred as the film material for the packaging film. Alternatively, when the hollow fiber membrane module 1 is pre-packaged and subjected to heat sterilization using an autoclave, the packaging film can also be a sterilization package. A sterilization package refers to a first part that is porous, allowing water vapor to pass through freely while preventing bacteria from entering the package from the outside. This first part is gas permeable. Alternatively, the packaging film can be constructed by bonding the outer edges of a film having the first part and a film having a second part such as high-density polyethylene or polypropylene. The second part has lower gas permeability than the first part.

[0039] The hollow fiber membrane module 1 of the present invention, including the preservation liquid, can have a total weight of 15 kg or more. Furthermore, the hollow fiber membrane module 1 contains portions where load tends to concentrate when the hollow fiber membrane module 1 is horizontally placed relative to its length, such as the corners of the nut 13. When stationary, the arrangement of the first portion of the packaging film between such portions and the mounting surface can potentially damage the durability of the packaging film due to crushing of the porous portion of the first portion. Therefore, it is preferable to provide the first portion outside the area of ​​the packaging film that comes into contact with the portion of the hollow fiber membrane module 1 where load tends to concentrate. In other words, it is preferable to provide the second portion in the area of ​​the packaging film that comes into contact with the portion of the hollow fiber membrane module 1 where load tends to concentrate.

[0040] like Figure 8 As shown, the hollow fiber membrane assembly 1 is packaged by a packaging film 23 such that the second part 22 is located within a range of at least 120° centered on the direction of rotation of the assembly housing 5 in the circumferential direction of the axis of the assembly housing 5 from the protruding direction of the upper nozzle 5a and the lower nozzle 5b by 90 degrees. Alternatively, as... Figure 9 As shown, the hollow fiber membrane assembly 1 is packaged with a packaging film 23 such that the second part 22 is located within a range of at least 60° centered on the direction opposite to the protruding direction of the upper nozzle 5a and the lower nozzle 5b in the circumferential direction of the axis of the assembly housing 5. When placing the hollow fiber membrane assembly 1, the orientation is usually adjusted so that the upper nozzle 5a and the lower nozzle 5b face the horizontal direction or the vertical direction. Alternatively, the hollow fiber membrane assembly 1 can also be placed such that the upper nozzle 5a and the lower nozzle 5b are in contact with the horizontal plane together with the assembly housing 1. Therefore, as described above, by packaging it in the packaging film 23, the possibility that the porous first part 24 is located below the vertical direction of the assembly housing 5, and the porous part 22 is clamped between the stationary part 24 and the assembly housing 5, can be reduced. The stationary part 24 is the ground, platform, inner bottom surface of the container, etc., on which the hollow fiber membrane assembly 1 is placed.

[0041] Alternatively, when the hollow fiber membrane assembly 1, packaged in the packaging film 23, is placed on the holding portion 24, if it is configured such that the compressive strength generated in the porous portion 22 is 10 kPa or less, the packaging can be performed such that the porous portion 22 is sandwiched between the hollow fiber membrane assembly 1 and the holding portion 24. For example, by placing it in a way that distributes the load to other parts, the load is not concentrated in the porous portion 22, and the compressive strength on the porous portion 22 can be reduced.

[0042] If it is the hollow fiber membrane module 1 of the above-described embodiment, it can prevent the thick-walled part of the hollow fiber membrane 3a from drying out during heat sterilization treatment, prevent bacterial growth during storage, and suppress damage to the hollow fiber membrane 3a caused by vibration during transportation, while meeting the water quality requirements of the biomedical field.

[0043] Next, the manufacturing method of the hollow fiber membrane module 1 in this embodiment will be described.

[0044] In the manufacturing method of the hollow fiber membrane module 1 in this embodiment, firstly, in the state before filling with the preservation liquid... Figure 1 The hollow fiber membrane module 1 shown contains sealed water and gas that have been sterilized through filtration within its housing 5. The sealed water is preferably pure water.

[0045] Here, the pure water of the present invention refers to water with reduced ionic content, a conductivity of 1 μS / cm or less, and filtered using a reverse osmosis membrane or ultrafiltration membrane. The number of particles 50 nm or larger contained in the pure water is preferably 10 or more per L and 200 or less per L.

[0046] Furthermore, regarding the organic matter content in the purified water, it is preferable to use water with a TOC content of 1 ppm or more and less than 50 ppm. Further, the concentration of metal ions in the purified water is preferably 10 ppb or more and less than 100 ppb, and the concentration of chloride ions in the purified water is preferably 25 ppb or more and less than 250 ppb.

[0047] Then, in the manufacturing method of the hollow fiber membrane module 1 in this embodiment, the hollow fiber membrane module 1 (shell 5) containing water that has been sterilized by filtration is subjected to a heat treatment at 80°C or higher and 125°C or lower. In this way, by further heating and sterilizing the water and gas that have been sterilized by filtration together, the water and gas inside the hollow fiber membrane module 1 can be transformed into a state in which no living bacteria exist.

[0048] It should be noted that water sterilization methods also include adding drugs, but in the case of hollow fiber membrane modules used in the biomedical field, in addition to the time required for cleaning before filtration operation and the use of pure water for cleaning, the drainage caused by cleaning will also increase. Therefore, heat-based sterilization without adding additional ingredients is preferred.

[0049] Furthermore, in the case of sterilizing water by heating as in this embodiment, most viable bacteria will be killed over time even at temperatures below 80°C. However, considering long-term storage of 3 months or more, it is preferable to heat to 80°C or higher to fully kill bacteria. Additionally, setting the heating temperature to 125°C or higher may cause damage due to differences in the thermal expansion coefficients of the components. From these perspectives, the preferred temperature for heat treatment is 80°C or higher and below 125°C, as in this embodiment. Furthermore, when the hollow fiber membrane module 1 of this embodiment is further sterilized using gamma rays after this heat treatment, by pre-performing heat sterilization at 85°C or higher and 95°C or lower, the internal state of the hollow fiber membrane module 1 can be kept constant, and sterilization can be achieved with minimal gamma ray irradiation.

[0050] Here, when the hollow fiber membrane module 1 is heated as described above, if the space inside the shell 5 is filled with water (in other words, Vtotal = Wtotal), the internal pressure of the module increases due to the thermal expansion of the water, potentially damaging the hollow fiber membrane 3a and the shell 5. One method to mitigate this pressure increase is to create a connection between the inside and outside of the module. However, in this case, the water, which expands due to the heating process, overflows to the outside and draws in external gas due to further volume contraction during cooling. Therefore, bacteria may be introduced into the module from the atmosphere. Furthermore, after cooling, the openings for piping connections of the hollow fiber membrane module 1 need to be replaced with blind flanges for final storage and transportation, complicating the operation.

[0051] In order to avoid these situations, in the manufacturing method of the hollow fiber membrane module 1 in this embodiment, in order to mitigate the pressure rise even if the water sealed in as the storage liquid expands due to heating, it is preferable to contain gas in at least one of the first space sp1, the second space sp2 and the third space sp3 of the hollow fiber membrane module 1 in a certain proportion.

[0052] Furthermore, during the heat sterilization process of the hollow fiber membrane module 1 containing water and gas, to prevent the hollow fiber membrane 3a from drying out, the relative humidity of the gas inside the hollow fiber membrane module 1 is preferably always 85% or higher, more preferably 90% or higher. When the relative humidity is below 85%, the hollow fiber membrane 3a may dry out, although this also depends on the total time. In particular, the hollow fiber membrane 3a located at the outermost periphery of the hollow fiber membrane bundle 3 is more likely to dry out. As a manufacturing method to maintain the relative humidity at a certain level or higher, the heating can be divided into multiple stages and performed in stages. Additionally, since the temperature rises from the second space sp2 inside the hollow fiber membrane module 1 during heating, it is preferable to increase the water content contained in the second space sp2. Furthermore, the hollow fiber membrane 3a located at the outermost periphery, slightly away from the portion that forms a whole with the hollow fiber membrane bundle 3, tends to dry out more easily. Thus, in order to prevent a portion of the hollow fiber membrane 3a from moving away from the rest of the hollow fiber membrane 3a as a whole, a mesh-like restrictive member can also be used to restrict the hollow fiber membrane bundle 3.

[0053] The method of heating the hollow fiber membrane module 1 can be appropriately selected. It can be heated from the outside of the hollow fiber membrane module 1 using dry air, humid heat, or pressurized steam. Alternatively, microwaves can also be used. In addition, during heating, the hollow fiber membrane module 1 can be horizontally positioned along its length, or it can be erected approximately vertically relative to the ground, or it can be heated while rotating about the length of the hollow fiber membrane module 1 as an axis.

[0054] Furthermore, the opening for piping connection provided in the hollow fiber membrane module 1 is preferably fitted with a blind flange before the start of heat treatment, or in other words, before the start of heat sterilization treatment. Alternatively, a sterile connector 20 may be installed. The connection is sealed by attaching a sterilization filter 21 to the sterile connector 20 to prevent bacterial inflow. To prevent the sterilization filter 21 from peeling off due to increased internal pressure in the hollow fiber membrane module 1, the pressure difference between the inside and outside of the hollow fiber membrane module 1 is 0 kPa before the start of heat treatment at an external temperature of 20°C, and the pressure difference between the inside and outside of the hollow fiber membrane module 1 during heat treatment is preferably within 20 kPa, more preferably within 10 kPa. The aforementioned heat treatment is preferably performed with the opening for piping connection sealed by a blind flange.

[0055] Next, refer to Figure 10An example of how the hollow fiber membrane module 1 of this embodiment is installed in the filtration device 100 for biopharmaceutical filtration will be described. Furthermore, the rinsing method and filtration method using the hollow fiber membrane module 1 of this embodiment will be described. It should be noted that in this filtration device 100 for biopharmaceutical filtration, a cross-flow filtration method utilizing internal pressure filtration is envisioned.

[0056] like Figure 10 As shown, the filtration device 100 is used, for example, to filter treated water containing cultured cells and target proteins. The filtration device 100 includes: a hollow fiber membrane assembly 1, a first filtered water collection pipe 101, a second filtered water collection pipe 102, a first valve 101a, a second valve 102a, a supply pipe 104, and a circulation pipe 105. The first filtered water collection pipe 101 and the second filtered water collection pipe 102 are respectively connected to the upper nozzle 5a and the lower nozzle 5b of the hollow fiber membrane assembly 1. The first filtered water collection pipe 101 is equipped with the first valve 101a. The second filtered water collection pipe 102 is equipped with the second valve 102a. One end of the supply pipe 104 is connected to a pipe 11a of the hollow fiber membrane assembly 1. Multiple ends of the supply pipe 104 are connected to a treated water tank 106. A pump 107 is installed on the supply pipe 104. Pump 107 pressurizes the treated water discharged from below the treated water tank 106 and supplies it to the hollow fiber membrane module 1. One end of the circulation piping 105 is connected to the piping 10a of the hollow fiber membrane module 1. The other end of the circulation piping 105 is connected to the upper part of the treated water tank 106. In the filtration device 100, the hollow fiber membrane module 1 is configured such that the axis of the housing 5 is parallel to the vertical direction, and the cover 10 is located above the cover 11.

[0057] In the filtration device 100, treated water is supplied from the treated water tank 106 to the hollow portion of the hollow fiber membrane 3a via the supply pipe 104 and the lower pipe 11a. The supplied treated water is filtered towards the outer surface of the hollow fiber membrane 3a, and the filtrate is recovered from the upper nozzle 5a with the lower nozzle 5b of the housing 5 closed. For example, the lower nozzle 5b is closed by closing the valve 102a, which is connected to the lower nozzle 5b via the second filtrate collection pipe 102 (described later). In addition, most of the supplied treated liquid is discharged as circulating water from the upper pipe 10a of the hollow fiber membrane bundle 3 and returned to the treated water tank 106 via the circulation pipe 105.

[0058] Then, when installing the hollow fiber membrane module 1 into the aforementioned filtration device 100, firstly, remove the blind plates 15, 16, 17, and 18 that seal the hollow fiber membrane module 1 as one of the embodiments, and discard the storage liquid sealed inside the hollow fiber membrane module 1 outside the piping of the water treatment device 100. Then, install the hollow membrane module 1 into the piping of the filtration device 100. Alternatively, during installation, the storage liquid inside the hollow fiber membrane module 1 can be discarded outside the system before installing it into the water treatment device 100.

[0059] In addition, the sterile connector 20 of the hollow fiber membrane module 1, which is sealed as another embodiment, is connected to the sterile connector of the piping installed to the filter device 100. By stripping the sterilized filter 21, the connection can be made while maintaining the sterility of the interior of the hollow fiber membrane module 100 and the piping of the filter device 100.

[0060] Here, the cleaning method for the hollow fiber membrane module 1 before filtration operation is described. After installing the hollow fiber membrane module 1 into the filtration device 100, pure water is introduced into the hollow portion (primary side) of the hollow fiber membrane 3a of the hollow fiber membrane module 1 through the lower pipe 11a from the supply pipe 104 at a specified pressure. In the hollow portion, most of the pure water is filtered in the hollow fiber membrane 3a and moves towards the outer surface side (secondary side) of the hollow fiber membrane 3a. Then, the filtered pure water is discharged from the upper nozzle 5a of the hollow fiber membrane module 1. Alternatively, drainage (filtered pure water) can also be performed from the lower nozzle 5b of the hollow fiber membrane module. Furthermore, the unit membrane area of ​​the filtration hollow fiber membrane module 1 is 5L / m². 2 Or 10L / m 2 At this time, all the pure water present on the outer surface (secondary side) of the hollow fiber membrane module is discharged from the lower nozzle 5b, and pure water is introduced again from the lower cover 11a to perform filtration-based cleaning, which can more effectively clean the inside of the hollow fiber membrane module 1. Furthermore, it can achieve a unit membrane area of ​​20 L / m² for the hollow fiber membrane module 1. 2 The TOC level of the filtered water after pure water filtration is suppressed to 500 ppb or below.

Example

[0061] The present embodiment is further described in detail below through examples and comparative examples, but the present embodiment is not limited to these examples.

[0062] Hollow fiber membrane modules were used in the following examples and comparative examples. Their characteristics and measurement methods are shown below.

[0063] [About Hollow Fiber Membranes] (Usage Example 1) Material: PVDF Pore ​​size: 0.1 μm (microfiltration membrane) Inner diameter / outer diameter: 1.4mm / 2.2mm (Usage Example 2) Material: Polysulfone Molecular weight cutoff: 6000 Da Inner diameter / outer diameter: 0.6mm / 1.0mm

[0064] [Methods for confirming bactericidal effect] Water samples were taken from the hollow fiber membrane module and the presence of viable bacteria was determined using an HPC total colony count sampling strip (model: MHPC10025) manufactured by Millipore.

[0065] [TOC Analysis of Preservative Solution] The TOC in the preservation solution was analyzed using the following instruments. TOC: Shimadzu Corporation TOC5000A

[0066] [Coefficient of linear expansion of component housing and blind flange] The coefficients of linear expansion of the component housing and blind plate were determined based on the thermomechanical analysis method of JIS K7197-1991.

[0067] Temperature measurement inside hollow fiber membrane modules A temperature sensor was inserted at the center of the hollow fiber membrane module along its length. The temperature sensor was configured to measure the temperature of the central portion of the hollow fiber membrane bundle. The measuring device used was a TR-7wb manufactured by T&D, and the temperature sensor element used was a stainless steel protective tube sensor (TR-1220).

[0068] [Relative humidity measurement inside hollow fiber membrane module] Relative humidity was measured using a thermo-hygrometer (LR8514) manufactured by HIOKI. The sensor element was installed by pre-drilling holes in a blind plate that blocked the nozzle or the blind plate that blocked the pipeline to allow the wiring to pass through. After the wiring was installed, it was sealed with epoxy resin, thereby measuring the relative humidity inside the hollow fiber membrane module.

[0069] [Methods for determining whether hollow fiber membranes are leaking and whether they are dry] After sterilization and storage for the specified period, the following steps are performed to confirm whether there is any leakage and whether the membrane is dry. First, drain the water from inside the hollow fiber membrane module and seal the pipeline on the primary side of the hollow fiber membrane module and one nozzle on the secondary side of the module with a blind flange. Then, pressurize air to a maximum of 0.2 MPa through another nozzle on the secondary side to check for any air bubbles generated from the opening of the hollow fiber membrane on the end face of the fixed part. A sample without air bubbles is considered to have neither leakage nor dryness. On the other hand, if air bubbles are confirmed to be generated, perform a hydrophilic treatment with alcohol and repeat the same leak check. If the air bubbles disappear this time, dryness is considered to have occurred. Conversely, if air bubbles continue to be generated after hydrophilic treatment, a leak is considered to have occurred in the hollow fiber membrane.

[0070] [Method for determining the pure water permeability of hollow fiber membrane modules] Pure water is introduced into the hollow fiber membrane module from its primary side (inner surface), and the amount of pure water permeating through the secondary side (outer surface) is measured. The water permeability of the hollow fiber membrane module at 25°C and 0.1 MPa is then calculated. The water permeability retention rate of the module is calculated based on the ratio of the water permeability of the hollow fiber membrane module before heat sterilization to that of the hollow fiber membrane module stored for 3 months after heat sterilization (described later).

[0071] [Water content and moisture percentage of the porous portion of the hollow fiber membrane] The weight of the hollow fiber membrane module after all water droplets inside the hydrophilized hollow fiber membrane module was measured. It was then dried at 50°C until no weight loss was observed, and the weight was measured again. The water content and moisture percentage of the porous portion of the hollow fiber membrane were calculated based on the difference between the two measurements.

[0072] [Moisture content on the primary and secondary sides of the hollow fiber membrane module] By filling the interior of a hydrophilic hollow fiber membrane module with pure water and then draining the water present on the primary and secondary sides, the maximum water content is calculated and used as the volume of each space. The water content shown in each embodiment is determined by introducing a fixed amount of water into each space, which is then defined as the water content of the primary and secondary spaces. The water content is calculated based on the ratio of the maximum water content to the water introduced into each space. Here, the primary side of the hollow fiber membrane module represents the first space, and the secondary side represents the second space. Furthermore, if the primary and secondary sides of the hollow fiber membrane module pre-contain water, the respective water content can be calculated according to the following steps. First, when measuring the water content of the primary side, all openings (upper and lower nozzles, upper and lower pipes) are sealed with blind flanges beforehand. With the hollow fiber membrane module configured with its length direction approximately perpendicular to the ground, the blind flanges on the lower and upper sides of the pipes on the primary side are opened, and after 5 minutes, the water drained from the lower side of the pipes is collected. At this time, the water content of the primary side, or in other words, the first space, can be determined based on the volume of the drained water. In addition, when measuring the water content in the secondary side, after sealing all openings (upper and lower nozzles, upper and lower pipes) with blind flanges beforehand, the hollow fiber membrane module is configured with its length direction approximately perpendicular to the ground. The blind flanges of the upper and lower nozzles are then opened, and water discharged from the lower nozzle is collected for 5 minutes. At this time, the water content in the secondary side space can be calculated based on the volume of discharged water.

[0073] [Outer and inner diameters of hollow fiber membranes] The porous hollow fiber membrane was sliced ​​into thin slices at a cross-section orthogonal to its length using a razor, and the outer and inner diameters were measured using a 100x magnifying glass. For a single sample, measurements were taken at 60° cut points at 30mm intervals along the length, and the average values ​​were used as the outer and inner diameters of the hollow fiber membrane.

[0074] [Storage test after 3 months of heat sterilization treatment] The heat-sterilized hollow fiber membrane modules were stored at room temperature for 3 months. Room temperature here refers to 18°C ​​or higher and 25°C or lower. Afterwards, for the hollow fiber membrane modules that met the storage period requirements, the aforementioned methods for determining leakage and dryness were applied to determine whether leakage occurred and whether the membranes were dry. Additionally, for the hollow fiber membrane modules that met the storage period requirements, the aforementioned method for confirming sterilization effectiveness was applied to determine whether viable bacteria had multiplied.

[0075] [Hot Cycling Storage Test from Room Temperature to 50°C] The heat-sterilized hollow fiber membrane module was horizontally arranged along its length inside a dryer. After heating at 50°C for 48 hours, it was allowed to stand in an ambient temperature environment (20°C to 24°C) for 24 hours. This temperature cycle was repeated as needed. For hollow fiber membrane modules that underwent 10, 40, and 70 cycles of this temperature cycle, the dryness determination method described above was applied to determine whether the membrane was dry.

[0076] [Random Vibration Durability Test] The following test was conducted with the hollow fiber membrane module bundled in a corrugated cardboard box. The corrugated cardboard box was placed on the test bench, and a bundle weighing 100 kg was stacked on top of the corrugated cardboard box. Under this condition, vibrations were varied in the frequency range from 1 Hz to 200 Hz, with the power spectral density (PSD) ranging from 0.000004 g. 2 / Hz should be appropriately changed to 0.02g 2 A vibration load was applied at / Hz, resulting in a total root mean square acceleration (PSD) of 0.53. Here, PSD represents the intensity of waves at various frequencies during random vibration. In this random vibration test, a vibration load was applied to the hollow fiber membrane module based on the ISTA 3A random vibration test procedure (Over the Road Trailer Spectrum). Furthermore, a vibration test was conducted without load, applied from the top of the packaging box containing the hollow fiber membrane module. Vibrations were varied within the frequency range of 1Hz to 200Hz, with the PSD level maintained at 0.00005g. 2 / Hz to 0.035g 2 The vibration load varied between / Hz. It was conducted according to the ISTA 3A random vibration test procedure (Pick-Up and Delivery Vehicle Spectrum), applying a vibration load that resulted in a total root mean square acceleration of 0.46 for the PSD. All test equipment was manufactured by Shinken Co., Ltd. (model: G9250-L). All tests were conducted at temperatures ranging from 20°C to 24°C. In the hollow fiber membrane modules that underwent vibration testing, the aforementioned method for determining leakage in hollow fiber membranes was applied to determine the presence or absence of leakage.

[0077] [25°C to 75°C thermal cycling durability test] After the heat-sterilized hollow fiber membrane module is installed on the device, cold water (maximum 25°C) and hot water (maximum 75°C) are alternately introduced every 30 minutes. After the target number of cycles is completed, the above-mentioned leakage detection method is used to check for any leaks from the membrane module.

[0078] [Rinsing Test] After heat-sterilized hollow fiber membrane modules are installed on the filtration unit, pure water is introduced from under the cover of the hollow fiber membrane module. The circulation flow rate is adjusted to 1 L / min and the filtration flow rate to 10 L / min, and a rinsing operation is performed. Every 5 minutes from the start of rinsing, samples are taken from the top of the hollow fiber membrane module cover and from the filtered water side. The TOC of the sampled pure water is analyzed using the same instrument as the preservation solution. By measuring the TOC, the amount of water dissolved from the hollow fiber membrane module is determined. As a target value for filtered water quality, the filtration rate is measured when the TOC of the filtered water side is below 500 ppb.

[0079] [Example 1] Pre-filtered ultrafiltration water was filled from the primary side to the secondary side of a hollow fiber membrane module using a PVDF microfiltration membrane. The module was then left to stand vertically for 5 minutes, allowing all water to drip out. Prescribed amounts of pure water were then added to both the primary and secondary sides to achieve the water content shown in Table 1 for the first and second spaces. All piping connections were then sealed with polysulfone blind flanges using clamps. The module was then horizontally placed in a dryer and subjected to a 90°C heat treatment for 24 hours. Slow cooling ensured that the sterilized water and gas were sealed within the hollow fiber membrane module. Various storage and durability tests were conducted using the sterilized hollow fiber membrane module. The results are shown in Table 1. After 3 months of storage at room temperature, a leak check was performed, confirming no leakage and membrane drying. The module's water permeability was measured, and the retention rate was 99% compared to before heat sterilization, indicating continued integrity. Pure water was collected from inside the hollow fiber membrane module to investigate the presence of viable bacteria, and it was confirmed that no viable bacteria were present. During the rinsing test on the filter unit, only 16 L / m² of membrane area was used. 2 Pure water can reduce the TOC on the filtered water side to 500 ppb. For hollow fiber membrane modules stored in an environment with temperature cycling from 20°C to 50°C, no drying of the hollow fiber membrane occurred after 10 cycles, but drying was confirmed after 40 cycles. The drying occurred at the outermost periphery of the hollow fiber membrane bundle. Furthermore, a leak check was performed on the hollow fiber membrane module after heat sterilization by applying vibration, and no leaks were confirmed, indicating that the hollow fiber membrane was not damaged. Additionally, a hot and cold cycling test was performed using the heat-sterilized hollow fiber membrane module. It should be noted that a hollow fiber membrane module with a separate fixing part and rectifier cylinder was used in Example 1. A leak check was performed after 500 cycles, and no leaks were detected.

[0080] [Example 2] The test used a hollow fiber membrane module of the same specifications as in Example 1. The difference was that the pure water content in the first space of the hollow fiber membrane module was set to Wfirst / Vfirst = 0.05, and the pure water content in the second space was set to Wsecond / Vsecond = 0.81. It was confirmed that in the hollow fiber membrane module of Example 2, which was stored at room temperature for 3 months after heat sterilization, the hollow fiber membrane did not dry out or leak. Furthermore, the module's water permeability retention rate was 101%, a satisfactory result. No viable bacteria were also confirmed. When performing a rinsing test on a filter device, only 15 L / m2 was used per unit membrane area. 2 Pure water was sufficient to reduce the TOC on the filtered water side to 500 ppb. For hollow fiber membrane modules stored in an environment with temperature cycling from 20°C to 50°C, it was confirmed that no drying of the hollow fiber membrane occurred after 10, 40, and 70 cycles. Furthermore, a leak check was performed on the hollow fiber membrane module after heat sterilization by applying vibration, and no leaks were found, confirming that the hollow fiber membrane was not damaged. Additionally, a hot and cold cycling test was performed using the heat-sterilized hollow fiber membrane module. In Example 2, a hollow fiber membrane module with a separate adhesive fixing part from the rectifier cylinder was also used. A leak check was performed after 500 cycles, and no leaks were detected.

[0081] [Example 3] The test used a hollow fiber membrane module of the same specifications as in Example 1. The difference was that the pure water content in the first space of the hollow fiber membrane module was set to Wfirst / Vfirst = 0.07, and the pure water content in the second space was set to Wsecond / Vsecond = 0.9. The heat-sterilized product was stored at room temperature for 3 months, confirming that the hollow fiber membrane did not dry out or leak. Furthermore, the module's water permeability retention rate was 100%, indicating no problems. No viable bacteria were also confirmed. When performing a rinsing test on the filter device, only 15 L / m2 was used per unit membrane area. 2 Pure water was sufficient to reduce the TOC on the filtered water side to 500 ppb. For hollow fiber membrane modules stored in an environment with temperature cycling from 20°C to 50°C, it was confirmed that no drying of the hollow fiber membrane occurred after 10, 40, and 70 cycles. Furthermore, a leak check was performed on the hollow fiber membrane module after heat sterilization by applying vibration, and no leaks were found, confirming that the hollow fiber membrane was not damaged. Additionally, a hot and cold cycling test was performed using the heat-sterilized hollow fiber membrane module. In Example 3, a hollow fiber membrane module with a separate fixing section and rectifier cylinder was also used. A leak check was performed after 500 cycles, and no leaks were detected.

[0082] [Example 4] The test used a hollow fiber membrane module of the same specifications as in Example 1. The difference was that the pure water content in the first space of the hollow fiber membrane module was set to Wfirst / Vfirst = 0.28, and the pure water content in the second space was set to Wsecond / Vsecond = 0.98. The heat-sterilized product was stored at room temperature for 3 months, confirming that the hollow fiber membrane did not dry out or leak. Furthermore, the module's water permeability retention rate was 103%, a satisfactory result. No viable bacteria were also confirmed. When performing a rinsing test on the filter device, only 15 L / m2 was used per unit membrane area. 2 Pure water was sufficient to reduce the TOC on the filtered water side to 500 ppb. For hollow fiber membrane modules stored in an environment with temperature cycling from 20°C to 50°C, it was confirmed that no drying of the hollow fiber membrane occurred after 10, 40, and 70 cycles. Furthermore, a leak check was performed on the hollow fiber membrane module after heat sterilization by applying vibration, and no leaks were found, and the hollow fiber membrane was not damaged. Additionally, a hot and cold cycling test was performed using the heat-sterilized hollow fiber membrane module. In Example 4, a hollow fiber membrane module with a separate fixing section and rectifier cylinder was also used. A leak check was performed after 500 cycles, and no leaks were detected.

[0083] [Example 5] The test used a hollow fiber membrane module of the same specifications as in Example 1. The difference was that the pure water content in the first space of the hollow fiber membrane module was set to Wfirst / Vfirst = 0.65, and the pure water content in the second space was set to Wsecond / Vsecond = 0.96. The heat-sterilized product was stored at room temperature for 3 months, confirming that the hollow fiber membrane did not dry out or leak. Furthermore, the module's water permeability retention rate was 99%, a satisfactory result. No viable bacteria were also confirmed. When performing a rinsing test on the filter device, only 14 L / m2 was used per unit membrane area. 2 Pure water was sufficient to reduce the TOC on the filtered water side to 500 ppb. For hollow fiber membrane modules stored in an environment with temperature cycling from 20°C to 50°C, it was confirmed that no drying of the hollow fiber membrane occurred after 10, 40, and 70 cycles. Furthermore, a leak check was performed on the hollow fiber membrane module after heat sterilization by applying vibration, and no leaks were found, indicating that the hollow fiber membrane was not damaged. Additionally, a hot and cold cycling test was performed using the heat-sterilized hollow fiber membrane module. In Example 5, a hollow fiber membrane module with a separate fixing section and rectifier cylinder was also used. A leak check was performed after 500 cycles, and no leaks were detected.

[0084] [Example 6] The test used a hollow fiber membrane module of the same specifications as in Example 1. The difference was that the pure water content in the first space of the hollow fiber membrane module was set to Wfirst / Vfirst = 0.92, and the pure water content in the second space was set to Wsecond / Vsecond = 0.95. The heat-sterilized product was stored at room temperature for 3 months, confirming that the hollow fiber membrane did not dry out or leak. Furthermore, the module's water permeability retention rate was 99%, a satisfactory result. No viable bacteria were also confirmed. When performing a rinsing test on the filter device, only 14 L / m2 was used per unit membrane area. 2 Pure water was sufficient to reduce the TOC on the filtered water side to 500 ppb. For hollow fiber membrane modules stored in an environment with temperature cycling from 20°C to 50°C, it was confirmed that no drying of the hollow fiber membrane occurred after 10, 40, and 70 cycles. Furthermore, a leak check was performed on the hollow fiber membrane module after heat sterilization by applying vibration, and no leaks were found, confirming that the hollow fiber membrane was not damaged. Additionally, a hot and cold cycling test was performed using the heat-sterilized hollow fiber membrane module. In Example 6, a hollow fiber membrane module with a separate fixing section and rectifier cylinder was also used. A leak check was performed after 500 cycles, and no leaks were detected.

[0085] [Comparative Example 1] The test used a hollow fiber membrane module of the same specifications as in Example 1. The difference was that the pure water content in the first space of the hollow fiber membrane module was set to Wfirst / Vfirst = 0.07, and the pure water content in the second space was set to Wsecond / Vsecond = 0.08. After heat sterilization, the sample was stored at room temperature for 3 months, and bubbles were confirmed to have formed in one hollow fiber membrane. Upon subsequent hydrophilization treatment and leak testing, no bubbles were generated, indicating that the hollow fiber membrane had dried out. Furthermore, the module's water permeability retention rate was 98%, a satisfactory result. No viable bacteria were also confirmed. During the rinsing test on the filter unit, only 18 L / m2 was used per unit membrane area. 2 Pure water can reduce the TOC on the filtered water side to 500 ppb. For hollow fiber membrane modules stored in an environment with temperature cycling from 20°C to 50°C, it was confirmed that bubbles were generated from the hollow fiber membrane at 3 locations during a leak check after 10 cycles. After a subsequent hydrophilic treatment, no bubbles were generated during a second leak check, indicating that the hollow fiber membrane had dried out.

[0086] [Comparative Example 2] The test used hollow fiber membrane modules of the same specifications as in Example 1. The difference was that a 3-month storage test at room temperature was conducted without subjecting the hollow fiber membrane modules to heat sterilization. No bubbles were generated during the leak check after 3 months of storage at room temperature. Furthermore, the module's water permeability retention rate was 99%, indicating no problems. Bacterial growth was confirmed during the check for viable bacteria. When the membrane was installed on the filter unit for rinsing tests, only 18 L / m² was used per unit membrane area. 2 Pure water can reduce the TOC on the filtered water side to 500 ppb.

[0087] [Comparative Example 3] The experiment used a hollow fiber membrane module of the same specifications as in Example 1. The difference was that the pure water content in the first space of the hollow fiber membrane module was set to Wfirst / Vfirst = 1.00, and the pure water content in the second space was set to Wsecond / Vsecond = 1.00. When the piping connections were sealed with blind flanges and heated at a set temperature of 90°C, the internal pressure of the hollow fiber membrane module rose to 560 kPa, resulting in a relatively high pressure experience on the outer shell.

[0088] [Example 7] The test used a hollow fiber membrane module of the same specifications as in Example 1. The difference was that the pure water content in the first space of the hollow fiber membrane module was set to Wfirst / Vfirst = 0.47, and the pure water content in the second space was set to Wsecond / Vsecond = 0.53. The heat-sterilized product was stored at room temperature for 3 months, confirming that the hollow fiber membrane did not dry out or leak. Furthermore, the module's water permeability retention rate was 97%, a satisfactory result. No viable bacteria were also confirmed. When performing a rinsing test on the filter device, only 16 L / m2 was used per unit membrane area. 2 Pure water was sufficient to reduce the TOC on the filtered water side to 500 ppb. For hollow fiber membrane modules stored in an environment with temperature cycling from 20°C to 50°C, it was confirmed that no drying of the hollow fiber membrane occurred after 10, 40, and 70 cycles. On the other hand, when a leak check was performed on the hollow fiber membrane module after heat sterilization by applying vibration, two leaks were confirmed. Furthermore, a hot and cold cycling test was performed using the hollow fiber membrane module after heat sterilization. In Example 7, a hollow fiber membrane module with a separate fixing part and rectifier cylinder was also used. A leak check was performed after 500 cycles, and no leaks were detected.

[0089] [Example 8] The test used a hollow fiber membrane module of the same specifications as in Example 1. The difference was that the pure water content in the first space of the hollow fiber membrane module was set to Wfirst / Vfirst = 0.28, and the pure water content in the second space was set to Wsecond / Vsecond = 0.31. The heat-sterilized product was stored at room temperature for 3 months, confirming that the hollow fiber membrane did not dry out or leak. Furthermore, the module's water permeability retention rate was 99%, a satisfactory result. No viable bacteria were also confirmed. When performing a rinsing test on the filter device, only 17 L / m2 was used per unit membrane area. 2 Pure water was sufficient to reduce the TOC on the filtered water side to 500 ppb. For hollow fiber membrane modules stored in an environment with temperature cycling from 20°C to 50°C, it was confirmed that no drying of the hollow fiber membrane occurred after 10, 40, and 70 cycles. A leak check was performed on the hollow fiber membrane module after heat sterilization by applying vibration, and it was confirmed that no bubbles were generated and no leaks occurred. Furthermore, a hot and cold cycling test was performed using the heat-sterilized hollow fiber membrane module. In Example 8, a hollow fiber membrane module with a separate fixing section and rectifier cylinder was also used. A leak check was performed after 500 cycles, and no leaks were detected.

[0090] [Example 9] The test used a hollow fiber membrane module of the same specifications as in Example 1. The difference was that the pure water content in the first space of the hollow fiber membrane module was set to Wfirst / Vfirst = 0.98, and the pure water content in the second space was set to Wsecond / Vsecond = 0.08. The heat-sterilized product was stored at room temperature for 3 months, confirming that the hollow fiber membrane did not dry out or leak. Furthermore, the module's water permeability retention rate was 98%, a satisfactory result. No viable bacteria were also confirmed. When performing a rinsing test on the filter device, only 16 L / m2 was used per unit membrane area. 2 Pure water can reduce the TOC on the filtered water side to 500 ppb. For hollow fiber membrane modules stored in an environment with temperature cycling from 20°C to 50°C, no bubbles were detected and no leaks occurred during leak checks after 10 cycles. However, leak checks after 40 and 70 cycles confirmed that the hollow fiber membrane had dried out. Leak checks were performed on hollow fiber membrane modules after heat sterilization by applying vibration, and no bubbles were detected and no leaks occurred. Furthermore, a hot and cold cycling test was conducted using hollow fiber membrane modules after heat sterilization. In Example 9, a hollow fiber membrane module with a separate fixing section and rectifier cylinder was also used. A leak check was performed after 500 cycles, and no leaks were detected.

[0091] [Example 10] The test used a hollow fiber membrane module of the same specifications as in Example 1. The difference was that the pure water content in the first space of the hollow fiber membrane module was set to Wfirst / Vfirst = 0.98, and the pure water content in the second space was set to Wsecond / Vsecond = 0.49. The heat-sterilized product was stored at room temperature for 3 months, confirming that the hollow fiber membrane did not dry out or leak. Furthermore, the module's water permeability retention rate was 100%, indicating no problems. No viable bacteria were also confirmed. When performing a rinsing test on the filter device, only 16 L / m2 was used per unit membrane area. 2 Pure water can reduce the TOC on the filtered water side to 500 ppb. For hollow fiber membrane modules stored in an environment with temperature cycling from 20°C to 50°C, leak checks were performed after 10, 40, and 70 cycles, confirming that no bubbles were generated from the hollow fiber membrane and no leaks occurred. On the other hand, when a leak check was performed after vibrating a hollow fiber membrane module that had undergone heat sterilization, bubbles were confirmed to have been generated from one point in the hollow fiber membrane, confirming a leak. Furthermore, a hot and cold cycling test was performed using a hollow fiber membrane module that had undergone heat sterilization. In Example 10, a hollow fiber membrane module with a separate fixing part and rectifier cylinder was also used. A leak check was performed after 500 cycles, and no leaks were detected.

[0092] [Example 11] Pre-filtered ultrafiltration water was filled from the primary side to the secondary side of a hollow fiber membrane module using a polysulfone ultrafiltration membrane. The module was then left to stand vertically relative to the ground for 5 minutes until all water dripped out. Prescribed amounts of pure water were then added to both the primary and secondary sides of the module to achieve a pure water content of Wfirst / Vfirst = 0.07 in the first space and Wsecond / Vsecond = 0.99 in the second space. All piping connections were then sealed with polysulfone blind flanges using clamps. The module was then horizontally placed in a dryer and subjected to a 90°C heat treatment for 24 hours. Slow cooling was then applied to seal the sterilized water and gas within the hollow fiber membrane module. Various storage and durability tests were conducted using the sterilized hollow fiber membrane module. The results are shown in Table 3. After 3 months of storage at room temperature, a leak check was performed, confirming no leaks and successful membrane drying. The water permeability of the module was measured, and the retention rate was 102% compared to before heat sterilization, indicating that it remained intact. Pure water was collected from inside the hollow fiber membrane module to investigate the presence of viable bacteria, which was confirmed to be absent. During rinsing tests on the filter unit, only 15 L / m² of membrane area was used. 2Pure water can reduce the TOC on the filtered water side to 500 ppb. For hollow fiber membrane modules stored in an environment with temperature cycling from 20°C to 50°C, it was confirmed that no drying of the hollow fiber membrane occurred after 10, 40, and 70 cycles. Furthermore, a leak check was performed on the membrane module after heat sterilization with vibration applied, confirming no leaks and no damage to the hollow fiber membrane. Additionally, a hot and cold cycling test was performed using the heat-sterilized hollow fiber membrane module. No leaks or other problems occurred after 500 cycles, but a leak was confirmed at point 1 during a leak check after 700 cycles. Disassembly revealed the leak location, starting at the part of the rectifier tube embedded in the fixing part.

[0093] [Example 12] The same hollow fiber membrane module as in Example 11 was used. The difference was that the pure water content in the first space of the hollow fiber membrane module was set to Wfirst / Vfirst = 0.53. The heat-sterilized product was stored at room temperature for 3 months, and it was confirmed that the hollow fiber membrane did not dry out or leak. Furthermore, the module's water permeability retention rate was 101%, a satisfactory result. No viable bacteria were also confirmed. During the rinsing test on the filter unit, only 14 L / m2 was used per unit membrane area. 2 Pure water was sufficient to reduce the TOC on the filtered water side to 500 ppb. For hollow fiber membrane modules stored in an environment with temperature cycling from 20°C to 50°C, it was confirmed that no drying of the hollow fiber membrane occurred after 10, 40, and 70 cycles. Furthermore, a leak check was performed on the membrane module after heat sterilization by applying vibration, confirming that no leaks occurred and the hollow fiber membrane was not damaged.

[0094] [Example 13] The membrane module used was the same hollow fiber membrane module as in Example 11. The difference was that the pure water content in the first space of the hollow fiber membrane module was set to Wfirst / Vfirst = 0.88, and the pure water content in the second space was set to Wsecond / Vsecond = 0.95. The heat-sterilized product was stored at room temperature for 3 months, and it was confirmed that the hollow fiber membrane did not dry out or leak. Furthermore, the module's water permeability retention rate was 99%, which was a satisfactory result. No viable bacteria were also confirmed to have been generated. During the rinsing test on the filter unit, only 13 L / m2 was used per unit membrane area. 2 Pure water was sufficient to reduce the TOC on the filtered water side to 500 ppb. For hollow fiber membrane modules stored in an environment with temperature cycling from 20°C to 50°C, it was confirmed that no drying of the hollow fiber membrane occurred after 10, 40, and 70 cycles. Furthermore, a leak check was performed on the membrane module after heat sterilization by applying vibration, confirming that no leaks occurred and the hollow fiber membrane was not damaged.

[0095] [Example 14] The membrane module used was the same hollow fiber membrane module as in Example 11. The difference was that the pure water content in the first space of the hollow fiber membrane module was set to Wfirst / Vfirst = 0.97, and the pure water content in the second space was set to Wsecond / Vsecond = 0.07. The heat-sterilized product was stored at room temperature for 3 months, and it was confirmed that the hollow fiber membrane did not dry out or leak. Furthermore, the module's water permeability retention rate was 97%, which was a satisfactory result. No viable bacteria were also confirmed to have been generated. During the rinsing test on the filter unit, only 17 L / m2 was used per unit membrane area. 2 Pure water can reduce the TOC on the filtered water side to 500 ppb. For hollow fiber membrane modules stored in an environment with temperature cycling from 20°C to 50°C, no leaks were detected during leak checks after 10 cycles. However, leak checks after 40 and 70 cycles confirmed that the hollow fiber membrane had dried out. Furthermore, leak checks were performed on membrane modules after heat sterilization followed by vibration, confirming no leaks and no damage to the hollow fiber membrane.

[0096] [Comparative Example 4] The membrane module used was the same hollow fiber membrane module as in Example 11. The difference was that the pure water content in the first space of the hollow fiber membrane module was set to Wfirst / Vfirst = 0.07, and the pure water content in the second space was set to Wsecond / Vsecond = 0.06. After storing the heat-sterilized product at room temperature for 3 months, it was confirmed that the hollow fiber membrane had dried out. Furthermore, the water permeability retention rate of the module was also 90%, a decrease of 10% compared to before heat sterilization. The generation of viable bacteria was confirmed. During the rinsing test performed on the filter device, only 18 L / m2 was used per unit membrane area. 2 Pure water can reduce the TOC on the filtered water side to 500 ppb. For hollow fiber membrane modules stored in an environment with temperature cycling from 20°C to 50°C, leak checks were performed after 10, 40, and 70 cycles, and it was confirmed that the hollow fiber membranes had dried out in all cases.

[0097] [Comparative Example 5] The same hollow fiber membrane module as in Example 11 was used. The difference was that the storage solution for the hollow fiber membrane module was changed from pure water to a 65 wt% glycerol aqueous solution. Additionally, the content of the glycerol aqueous solution in the first space of the hollow fiber membrane module was set to Wfirst / Vfirst = 0.05, and the content of the glycerol aqueous solution in the second space was set to Wsecond / Vsecond = 0.04. After heat-sterilized products were stored at room temperature for 3 months, the module permeability retention rate remained at 101%, which is within a acceptable range. No viable bacteria were confirmed to have formed. When performing a rinsing test on the filter unit, a permeate flow rate of 200 L / m200 was required per unit membrane area. 2 Only pure water can reduce the TOC on the filtered water side to 500 ppb.

[0098] [Example 15] The test used a hollow fiber membrane module of the same specifications as in Example 1. The differences were that the pure water content in the first space of the hollow fiber membrane module was set to Wfirst / Vfirst = 0.12, the pure water content in the second space was set to Wsecond / Vsecond = 0.18, and a sterile connector was used. The sterile connector used was a sterile connector (AQS33012HT) manufactured by CPC Corporation. Furthermore, for the hollow fiber membrane module of Example 15, it was wrapped in a sterilization bag (trade name: Cleanpeak Easy-Tear Bag) before heat treatment. One side of the sterilization bag used a nonwoven fabric (Tybek1073b) with excellent water vapor permeability, and the other side used a high-density polyethylene film. During settling in the heat treatment apparatus, the high-density polyethylene film was positioned between the hollow fiber membrane module and the mounting surface of the heat treatment apparatus, and the nonwoven fabric side was positioned on top of the hollow fiber membrane module. This is a measure to prevent excessive compression of the nonwoven fabric surface, which could damage the porous parts. Afterwards, steam sterilization at 125°C was performed. The treated product was stored at room temperature for 3 months, confirming that the hollow fiber membrane did not dry out or leak. Furthermore, the module's water permeability retention rate was 98%, a satisfactory result. No viable bacteria were also confirmed. During rinsing tests on the filter unit, only 17 L / m² was used per unit membrane area. 2Pure water was sufficient to reduce the TOC on the filtered water side to 500 ppb. For hollow fiber membrane modules stored in an environment with temperature cycling from 20°C to 50°C, it was confirmed that no drying of the hollow fiber membrane occurred after 10, 40, and 70 cycles. Furthermore, a leak check was performed on the membrane module after heat sterilization by applying vibration, and no leaks were found, confirming that the hollow fiber membrane was not damaged. Additionally, a hot and cold cycling test was performed using the heat-sterilized hollow fiber membrane module. In Example 15, a hollow fiber membrane module with a separate fixing section and rectifier cylinder was also used. A leak check was performed after 500 cycles, and no leaks were detected.

[0099] Table 1 Membrane material - PVDF PVDF PVDF PVDF PVDF MF or UF- MF MF MF MF MF Inner diameter mm 1.4 1.4 1.4 1.4 1.4 outer diameter (mm) 2.2 2.2 2.2 2.2 2.2 Number of film roots 2050 2050 2050 2050 2050 Shell material - polysulfone polysulfone polysulfone polysulfone polysulfone Tube inner diameter mm 130 130 130 130 130 <![CDATA[Sum of cross-sectional areas of fiber outer diameters mm 2 > 7793 7793 7793 7793 7793 <![CDATA[Sum of pipe inner diameter cross-sectional area mm 2 > 13273 13273 13273 13273 13273 Sum of fiber outer diameter cross-sectional areas / Sum of tube inner diameter cross-sectional areas * 100% 58.7 58.7 58.7 58.7 58.7 Nozzle and cover sealing components - blind plate blind plate blind plate blind plate blind plate The ratio of linear expansion coefficients of the component housing to the blind plate 1 1 1 1 1 Sterilization package - none none none none none Heating method - Dryer heating No heating Dryer heating Dryer heating Dryer heating Mo configuration during heating Horizontal placement Horizontal placement Horizontal placement Horizontal placement Horizontal placement V First L 4.22 4.22 4.22 4.22 4.22 V Second L 4.91 4.91 4.91 4.91 4.91 V-hole L 3.61 3.61 3.61 3.61 3.61 V total L 12.74 12.74 12.74 12.74 12.74 W First L 0.30 0.55 0.55 0.20 0.30 W Second L 0.40 0.65 0.65 3.98 4.42 Whole L 3.10 3.61 3.30 3.57 3.54 W total L 3.80 4.81 4.50 7.75 8.26 W first / V first 0.07 0.13 0.13 0.05 0.07 W second / V second 0.08 0.13 0.13 0.81 0.90 Mr. W / Mr. V — 0.30 0.38 0.35 0.61 0.65 W-hole / V-hole — 0.86 1.00 0.91 0.99 0.98 W_first / V_first<W_second / V_second ○ ○ ○ ○ ○ 0.8≦W_second / V_second≦1 × × × ○ ○ Gap between rectifier tube and potting section have have have have none Temperature reached during heating ℃ 90 - 90 90 85 Minimum relative humidity rt% during temperature rise 67 - 81 86 87 Internal pressure of the component at the set temperature (kPa) 100 - 100 105 90 TOCppm 46 46 46 42 38 After heat sterilization for 3 months, store at room temperature and check for film drying. have none none none none After heat sterilization for 3 months - store at room temperature - check for membrane leakage - none none none none none After heat sterilization treatment for 3 months - stored at room temperature - water permeability retention rate % 98 99 99 101 100 After heat sterilization for 3 months, store at room temperature to check for bacterial growth. none have none none none After 10 cycles of thermal cycling at 20°C to 50°C, is there any film drying? have none none none none Thermal cycling at 20°C to 50°C - after 40 cycles - is there any film drying? have have have none none Thermal cycling at 20°C to 50°C for 70 cycles - Did film drying occur? have have have none none After the vibration load test, is there any leakage from the membrane? none none none none none Check for leaks after a thermal cycling test from 20°C to 75°C. none none none none none

[0100] Table 2

[0101] Table 3

[0102] Table 4 [Label Explanation]

[0103] 1 Hollow fiber membrane module 3 Hollow fiber membrane bundles 3a Hollow fiber membrane 5 Component Housing 5a Upper nozzle 5b Lower nozzle 10, 11 Cover 10a and 11a piping 12 O-rings 13 nuts 14 Fixing part Blind plates 15, 16, 17, and 18 19a and 19b rectifier tubes 20 Sterile Connectors 21. Sterilization Filter 22 Part Two 23 Packaging film 24 Part 1 25. Static Section 100 filtration device 101 First filtered water collection pipe 102 Second Filter Water Collection Pipe 101a First Valve 102a Second Valve 104 Supply Piping 105 Circulation Piping 106 Water tanks being treated sp1 First Space sp2 Second Space SP3 Third Space YY First Blind Board ZZ Second Blind Plate

Claims

1. A hollow fiber membrane module, characterized in that, Hollow fiber membrane bundles, consisting of multiple hollow fiber membranes bundled together, are housed within the component housing. In a hollow fiber membrane module where both ends of the hollow fiber membrane bundle are integrated with the module housing via a potting material, The porous portion of the hollow fiber membrane bundle contains 90% or more of water, i.e., a preservation solution, in which no live bacteria are present. The space inside the component housing is filled with gas and the preservation liquid, which contain no living bacteria. It also includes: a pair of fixing portions at both ends of the hollow fiber membrane bundle within the component housing, formed by a potting material sealing the gaps between the outer surfaces of the hollow fiber membranes and between the outer surfaces and the inner surface of the component housing; and a pair of rectifier tubes located at the center side of the component housing along its length, respectively surrounding both ends of the hollow fiber membrane bundle, wherein... In the rectifier cylinder, the separation width between the end located on the fixed part side and the fixed part is 1 mm or more and 20 mm or less.

2. The hollow fiber membrane module according to claim 1, characterized in that, When the openings for piping connections on the component housing are sealed by a sealing member. Let the volume of the first space surrounded by the inner surface of the cover installed on the component housing, the end face of the potting material, and the inner surface and end faces of the hollow fiber membrane be defined as Vfirst. Let the volume of the second space surrounded by the inner surface of the component housing, the end face of the potting material, and the outer surface of the hollow fiber membrane be defined as Vsecond. The volume of the third space formed by the porous portion of the hollow fiber membrane is defined as V_pore. Let the total volume of Vfirst, Vsecond, and Vhole be Vtotal. Let the volume of the preservation fluid existing in the first space be W_first. Let the volume of the preservation liquid existing in the second space be W_second. Let the total volume of the preservation fluid present in the third space be W_hole. And when the total volume of Wfirst, Wsecond, and Whole is set as Wtotal, the following equation (1) is satisfied. 0.35 ≦ W_total / V_total ≦ 0.95 ・・・(1).

3. The hollow fiber membrane module according to claim 2, characterized in that, The ratio of Wfirst to Vfirst is less than or equal to the ratio of Wsecond to Vsecond.

4. The hollow fiber membrane module according to claim 2, characterized in that, The ratio of W second to V second is greater than or equal to 0.8 and less than or equal to 1.

5. The hollow fiber membrane module according to claim 1 or 2, characterized in that, The TOC of the preservation solution contained within the component housing is 1 ppm or higher and less than 50 ppm.

6. The hollow fiber membrane module according to claim 1 or 2, characterized in that, The concentration of metal ions in the preservation solution contained within the component housing is 10 ppb or more but less than 100 ppb.

7. The hollow fiber membrane module according to claim 1 or 2, characterized in that, All openings for piping connections located in the component housing are sealed by blind flanges. The linear expansion coefficient of the raw material used in the blind flange is between 0.95 and 1.05 times that of the component housing.

8. The hollow fiber membrane module according to claim 1, characterized in that, It is packaged in a packaging film having at least a portion of a first portion that is permeable to gas.

9. The hollow fiber membrane module according to claim 8, characterized in that, The component housing is cylindrical, and at least a portion of the opening for piping connection provided in the component housing protrudes in a direction orthogonal to the length direction of the component housing. The second portion, which is packaged by the packaging film such that the gas permeability of the packaging film is lower than that of the first portion, is located within a range of 120° centered on the direction of rotation of the protruding direction of the opening in the circumferential direction of the component housing, or within a range of 60° centered on the opposite direction of the protruding direction.

10. The hollow fiber membrane module according to claim 1 or 2, characterized in that, A sterile connector is installed in the piping connection opening located on the component housing. The sterile connector includes a sterilization filter. One end face of the sterilization filter is in direct contact with the space inside the hollow fiber membrane module.

11. The hollow fiber membrane module according to claim 1 or 2, wherein, The raw materials for the hollow fiber membrane are selected from polysulfone, polyethersulfone, polyacrylonitrile, polyphenylsulfone, polyimide, polyetherimide, polyamide, polyetherketone, polyetheretherketone, polyethylene, polypropylene, poly(4-methylpentene), ethylene-vinyl alcohol copolymer, cellulose, cellulose acetate, polyvinylidene fluoride, ethylene-tetrafluoroethylene copolymer, polytetrafluoroethylene, or composite raw materials thereof.

12. The hollow fiber membrane module according to claim 1 or 2, wherein, The potting material is selected from epoxy resin, vinyl ester resin, polyurethane resin, unsaturated polyester resin, olefin polymer, silicone resin, fluorinated resin or a combination thereof.

13. The hollow fiber membrane module according to claim 11, wherein, The raw materials for the hollow fiber membrane are selected from polyvinylidene fluoride, polysulfone, polyethersulfone, and polyphenylsulfone.

14. The hollow fiber membrane module according to claim 12, wherein, The potting material is epoxy resin.

15. The hollow fiber membrane module according to claim 1 or 2, wherein, The hollow fiber membrane has an inner diameter of 50 μm to 3000 μm.

16. A method for manufacturing a hollow fiber membrane module, characterized in that, A hollow fiber membrane bundle, consisting of multiple hollow fiber membranes bundled together, is inserted into the component housing. In a hollow fiber membrane module where both ends of the hollow fiber membrane bundle are integrated with the module housing via a potting material, The porous portion of the hollow fiber membrane bundle is filled with 90% or more of water, i.e., a preservation solution, in which no live bacteria are present. The space within the component housing is filled with a gas devoid of living bacteria and the preservation liquid, wherein, When the piping connections on the component housing are sealed by a blind flange, the volume of the first space surrounded by the inner surface of the cover installed on the component housing, the end face of the potting material, and the inner surface and end faces of the hollow fiber membrane is defined as Vfirst; the volume of the second space surrounded by the inner surface of the pipe portion of the component housing, the end face of the potting material, and the outer surface of the hollow fiber membrane is defined as Vsecond; the volume of the third space formed by the porous portion of the hollow fiber membrane is defined as Vhole; the total volume of Vfirst, Vsecond, and Vhole is defined as Vtotal; the volume of water in the first space is defined as Wfirst; the volume of water in the second space is defined as Wsecond; the total volume of water in the third space is defined as Whole; and the total volume of Wfirst, Wsecond, and Whole is defined as Wtotal. Therefore, the total volume inside the hollow fiber membrane module is adjusted to a relationship of 0.35 ≤ Wtotal / Vtotal ≤ 0.

95. Furthermore, with the piping connection openings sealed, the water and gas in the hollow fiber membrane module are transformed into a state devoid of living bacteria through heating treatment at 80ºC or higher and 125ºC or lower. Within the component housing, at both ends of the hollow fiber membrane bundle, a pair of fixing portions are provided, consisting of a potting material that seals the gap between the outer surfaces of the hollow fiber membrane and each other and between the outer surfaces and the inner surface of the component housing; and a pair of rectifier tubes are provided on the central side of the component housing along the length direction of the fixing portions, such that the separation width between the end of the rectifier tube located on the fixing portion side and the fixing portion is 1 mm or more and 20 mm or less.

17. The method for manufacturing a hollow fiber membrane module according to claim 16, characterized in that, During the process of heating the hollow fiber membrane module containing the water and the gas, the relative humidity inside the module housing is maintained at 85% or higher.

18. The method for manufacturing a hollow fiber membrane module according to claim 16 or 17, characterized in that, In the process of heating the component housing containing the water and the gas, the exterior of the hollow fiber membrane component is heated using dry air.

19. The method for manufacturing a hollow fiber membrane module according to claim 16 or 17, characterized in that, In the hollow fiber membrane module with a sterile connector installed at the piping connection opening in the module housing, the pressure difference between the inside of the module housing and the outside of the module housing at 20ºC is 0 kPa before the start of heat treatment. During heat treatment, the pressure difference between the inside and outside of the component housing, separated by the sterilization filter of the aseptic connector, is 20 kPa or less.

20. The method for manufacturing a hollow fiber membrane module according to claim 16 or 17, characterized in that, In the process of heating the component housing containing the water and the gas... Heating is performed with the piping connection openings in the component housing sealed by a blind flange.

21. The method for manufacturing a hollow fiber membrane module according to claim 16 or 17, characterized in that, The hollow fiber membrane assembly is heat-treated while encased in a packaging film having at least a portion of a first portion that is gas-permeable.

22. The method for manufacturing a hollow fiber membrane module according to claim 21, characterized in that, The component housing is cylindrical, and at least a portion of the opening for piping connection provided in the component housing protrudes in a direction orthogonal to the length direction of the component housing. In the process of heating the hollow fiber membrane assembly containing the water and the gas, a second portion, packaged by the packaging film such that the gas permeability of the packaging film is lower than that of the first portion, is located within a range of 120° centered on the direction of rotation of 90° from the protruding direction of the opening, or within a range of 60° centered on the opposite direction of the protruding direction, in the circumferential direction of the axis of the assembly housing.

23. A cleaning method for a hollow fiber membrane module, characterized in that, When cleaning the interior of a hollow fiber membrane module manufactured by the manufacturing method of claim 16 or 17 using filtration cleaning, By measuring the unit membrane area of ​​the hollow fiber membrane at 20 L / m² 2 Filter pure water of 500 ppb or less to achieve a TOC of 500 ppb or less.

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