Sterilisation method for a hollow fibre membrane filter

Abstract

The present invention relates to a method for sterilising a hollow fibre membrane filter with a sterilising fluid, such as e.g. water or water vapour, said method comprising: a rinsing step; a sterilisation step; and a leakage test for ensuring greater certainty of the sterility of the hollow fibre membrane filter.

Description

Sterilization process for a hollow fiber membrane filter

[0001] The subject of the present application is a sterilization process for hollow fiber membrane filters used for extracorporeal blood treatment of patients with kidney disease.

[0002] The hollow fiber membranes used for blood purification are often made of polysulfone (PSU) and polyvinylpyrrolidone (PVP), as these materials have been found to be preferentially hemocompatible and are therefore medically preferred in blood treatment, especially in hemodialysis.

[0003] In the production of such hollow fiber membranes, a spinning dope is extruded through a nozzle to form a hollow filament and introduced into a coagulation bath, usually consisting of water. To form the pore structure, an aqueous coagulant containing aprotic solvents such as dimethylacetamide, N-methylpyrrolidone, dimethylformamide or dimethyl sulfoxide is used. The resulting hollow fiber membrane is then passed through rinsing baths, dried and taken up on a reel. The hollow fiber membranes can be removed from the reel in the form of hollow fiber membrane bundles. To construct hollow fiber membrane filters, such hollow fiber membrane bundles are placed in a housing, preferably a cylindrical housing. The ends of the hollow fiber membrane bundle are embedded in a potting compound and the open ends of the hollow fibers are exposed.The potting compound forms a sealing area between the interior of the hollow fiber membranes, the housing, and the area surrounding the hollow fiber membranes. This creates a first chamber in the finished hollow fiber membrane filter, which encompasses the inflow and outflow areas of the ends of the hollow fiber membrane bundle and also the interior of the hollow fiber membranes. A second chamber is formed in the space between the hollow fiber membranes and between the housing wall and the hollow fiber membranes. Fluid inlets on the housing of the hollow fiber membrane filter enable the supply and discharge of fluids. Discharge of liquids and fluids to the first and / or second chamber of the hollow fiber membrane filter.

[0004] Hollow-fiber membrane filters intended for extracorporeal blood treatment typically have a first and a second fluid inlet in the first chamber of the filter module, as well as a first and a second fluid inlet in the second chamber of the filter module. Fluids, particularly liquids or gases, can thus be supplied or discharged via the first inlet of a chamber of the hollow-fiber membrane filter, depending on the flow direction, or via the second inlet of a chamber of the hollow-fiber membrane filter, depending on the flow direction.

[0005] For hollow fiber membrane filters intended for medical purposes, particularly for the blood treatment of patients with kidney disease, the manufacturing process of the hollow fiber membranes and the filter construction are usually followed by one or more rinsing and sterilization steps to clean the hollow fiber membranes and sterilize them for medical use.

[0006] Corresponding processes are known in the prior art in which the hollow fiber membranes in hollow fiber membrane filters are subjected to rinsing and sterilization steps. In particular, heat sterilization with water or steam in hollow fiber membrane filters is a well-known sterilization method for hollow fiber membranes and hollow fiber membrane filters. Heat sterilization refers to sterilization with fluids (e.g., water or steam, or mixtures thereof) above a temperature of 100°C. Heat sterilization with predominantly pure steam is also called steam sterilization.

[0007] A corresponding method for sterilizing dialyzers is described in DE 39 36 785 C1. According to this method, the dialyzers are first subjected to a rinsing process and then to a sterilization process. During the sterilization process, the dialyzer is rinsed with water or steam heated to over 121 °C. The heat sterilization performed according to DE 39 36 785 C1 has proven to be superior to the other sterilization methods mentioned, both in terms of equipment and process technology.

[0008] WO2018 / 204498A9 describes a sterilization process for hollow fiber membrane filters comprising hollow fiber membranes made of polysulfone and polyvinylpyrrolidone. The sterilization process described uses a process step in which steam is passed over the membrane wall by adjusting the pressure conditions in the first and second chambers of the hollow fiber membrane filter.

[0009] The processes known in the prior art are designed so that further process steps follow the actual sterilization step. In particular, in these processes the leakage test of the hollow fiber membrane filter was carried out after the sterilization step. The leakage test performed during steam sterilization of hollow fiber membrane filters is usually carried out as a so-called "bubble point test." In this test, the second chamber of the hollow fiber membrane filter defined above is filled with sterile compressed air or, alternatively, sterile compressed air flows through it. Ultrapure water is filled or flows through the second chamber of the hollow fiber membrane filter. In an upstream step, the pores of the hollow fiber membranes are filled with water. The pressure of the sterile compressed air in the "bubble point test" is selected such that the surface tension of the water in the pores is not overcome and the water remains in the pores.However, if leaks exist between the first and second chambers of the hollow fiber membrane filter, the sterile compressed air will overflow into the first chamber at the set pressure and be expelled from the first chamber with the flowing ultrapure water. An air bubble detector connected to a discharge line from the first chamber of the hollow fiber membrane filter can detect the overflowing sterile compressed air, and the hollow fiber membrane filter can be sorted out accordingly during the process flow.

[0010] The disadvantage is that, in the current state of the art, this leakage test is performed after the actual sterilization step. Therefore, there is a need to further improve the sterility of the filter. Furthermore, the integrity of a hollow-fiber membrane filter, and thus the performance of the leakage test, is of utmost importance, as hollow-fiber membrane filters that exhibit a leak due to production-related defects are not permitted for medical use. OBJECT OF THE INVENTION

[0011] In view of the problems prevailing in the prior art, the object was therefore to provide a method for the sterilization of hollow fiber membrane filters, which is based on the principle of steam and heat sterilization and has a high sterilization quality, but also ensures the integrity of a hollow fiber membrane filter. SUMMARY OF THE INVENTION

[0012] The object of the present invention is achieved by a method according to claim 1. Claims 2 to 14 represent preferred embodiments of the method. DESCRIPTION OF THE INVENTION

[0013] In the following, the present invention is described using individual embodiments and illustrated with reference to Figs. 1 to 4.

[0014] The present invention relates to a method for sterilizing a hollow fiber membrane filter comprising a plurality of hollow fiber membranes sealed at the ends in the housing of the hollow fiber membrane filter such that a first space is created that encompasses the interior of the hollow fiber membranes, and a second space is created that encompasses a space between the hollow fiber membranes, wherein the hollow fiber membrane filter has at least two fluid inlets connected to the first space and at least two fluid inlets connected to the second space, and wherein the fluid inlets are prepared to be connected to a sterilization device. The method comprises at least the steps: Flushing the hollow fiber membrane filter with a fluid, in particular water, wherein the flushing fluid is passed through the first and second chambers of the hollow fiber membrane filter via a selection of fluid inlets, performing a leakage test, Sterilizing the hollow fiber membrane filter with a sterilizing fluid, in particular heated water or steam, wherein the sterilizing fluid is passed through the first and second spaces of the hollow fiber membrane filter via a selection of the fluid inlets, characterized in that the leakage test is carried out before the sterilizing step.

[0015] In a further embodiment, the method according to the invention is characterized in that in the leakage test sterile compressed air is introduced into, in particular passed through, the second chamber of the hollow fiber membrane filter and ultrapure water is introduced into, in particular passed through, the first chamber of the hollow fiber membrane filter and the pressure in the second chamber is higher than in the first chamber.

[0016] According to the method according to the invention, the sterilization step takes place after the leak test. This ensures that no further rinsing steps, e.g., as part of a leak test, are carried out after the sterilization step, which could recontaminate the hollow fiber membrane filter with germs.

[0017] Fig. 1 shows a schematic representation of the rinsing step of the method according to the invention. It shows a hollow fiber membrane filter 101, which has two fluid inlets 102a, 102b, which form an access to the second space 120 of the hollow fiber membrane filter 101. Only one of a plurality of hollow fiber membranes is shown schematically in Fig. 1. 103a, 103b indicate the fluid inlets, which form an access to the first space 110 of the hollow fiber membrane filter. The fluid inlets 102a, 102b, 103a, 103b are connected via connecting devices 150A, 150B, 150C, 150D to a Connected to a sterilization device, which is not shown in Fig. 1. A stream of ultrapure water is provided via the sterilization device, which is introduced into the second and first chambers 120, 110 of the hollow fiber membrane filter 101 via the connection devices 150A, 150B and the fluid inlets 102b, 103b. According to the embodiment of Fig. 1, ultrapure water flows through the first and second chambers 110, 120. The hollow fiber membrane filter is thus preconditioned for the subsequent steps of the sterilization process. The characteristics of ultrapure water within the meaning of the present application are described in the European Pharmacopoeia "European Pharmacopoeia PH. EUR. 04 / 2017:0169".

[0018] According to the illustrated embodiment, the temperature of the incoming ultrapure water is 85°C. However, depending on the design of the hollow fiber membrane filter, other temperatures between 50 to 120°C, 50 to 95°C, 60 to 90°C, 65 to 90°C, or 70 to 90°C can generally be set for the ultrapure water in the rinsing step. The ultrapure water leaves the first and second chambers 110, 120 via the fluid inlets 103a, 102a and the connection devices 150C, 150D and is discharged as wastewater.

[0019] The duration of the rinsing step is preferably 40 seconds (s). Depending on the design of the hollow fiber membrane filter, an alternative duration of the rinsing step can be provided, e.g., 20 to 60 s, 30 to 60 s, 35 to 50 s, or 35 to 45 s.

[0020] During the rinsing step, all air is expelled from the hollow fiber membrane filter, ie the air in the first and second chambers 110, 120 of the hollow fiber membrane filter and in particular also the air from the pores of the membrane wall of the hollow fiber membranes are expelled.

[0021] Fig. 2 shows a schematic representation of the leakage test step of the method according to the invention. In the embodiment shown, the leakage test is carried out as a so-called "bubble point test." The arrangement of the hollow fiber membrane filter, the connection devices 150A, 150B, 150C, 150D in conjunction with the The sterilization device (not shown in Fig. 2) is the same as in Fig. 1. In the schematically illustrated process step of the leakage test, ultrapure water is made available via the sterilization device and introduced into the first chamber 110 of the hollow fiber membrane filter via the connection device 150B and the fluid inlet 103b. In this embodiment, the ultrapure water has a temperature of 50°C and a pressure of 1 bar. The temperature can vary depending on the design of the hollow fiber membrane filter and can be between 30 and 70°C, 40 and 60°C, or 45 and 55°C. The pressure can accordingly be between 0.5 and 1.5 bar or between 0.9 and 1.1 bar. Sterile compressed air is flowed into the second chamber of the hollow fiber membrane filter via the connection device 150D and the fluid inlet 102a.The pressure of the sterile compressed air is 2 bar in the illustrated embodiment and can vary between 1.5 and 3.5 bar depending on the design of the hollow fiber membrane filter and the pore size in the hollow fiber membranes. The ultrapure water is passed through the first chamber 110 and via the fluid inlet 103a. and the connection device 150C. The sterile compressed air is passed through the second chamber 120 of the hollow fiber membrane filter 101 and discharged via the fluid inlet 102b and the connection device 150A. In the embodiment shown, sterile compressed air and ultrapure water are passed through the respective second and first chambers 120, 110 of the hollow fiber membrane filter in countercurrent. If a leak exists between the first chamber and the second chamber, sterile compressed air passes from the second chamber 120 into the first chamber 110 and can be detected. Accordingly, an optical detector is attached to the waste line 104, wherein the waste line is attached to the connection device 150C and is in fluid communication with the first chamber 110 of the hollow fiber membrane filter 101.The compressed air that enters the first chamber in the event of a leak is expelled as air bubbles with the ultrapure water from the first chamber of the hollow fiber membrane filter and can be optically detected in the wastewater line by appropriate detectors.

[0022] If the hollow fiber membrane filter has been determined to be leak-free, the second chamber 120 of the hollow fiber membrane filter 101 is filled with air and the first chamber with ultrapure water after the leak test. Furthermore, the pores of the membrane wall of the hollow fiber membranes are also filled with ultrapure water.

[0023] Fig. 3 shows a schematic representation of the sterilization step of the method according to the invention. The arrangement of the hollow fiber membrane filter, the connecting devices 150A, 150B, 150C, 150D in connection with the The sterilization device (not shown in Fig. 3) is the same as in Fig. 1 and Fig. 2. In the sterilization step, ultrapure water vapor is introduced into the first chamber 110 and the second chamber 120 of the hollow fiber membrane filter 101 via the connection devices 150C and 150D and the fluid inlets 103a and 102a. The ultrapure water vapor is provided via the sterilization device and, according to the embodiment shown, has a temperature of 123°C and a pressure of 1.3 bar. Depending on the design of the hollow fiber membrane filter, other pressures and temperatures can also be provided to ensure an optimal sterilization result. In particular, pressures of 1.1 to 3 bar or 1.1 to 2.5 bar or 1.1 to 2 bar, or 1.1 to 1.8 bar or 1.2 to 1.6 bar can also be provided for the sterilization step. Alternative Temperatures of the ultrapure water vapor can range from 105 to 150°C, or from 110 to 140°C, or from 115 to 130°C. The ultrapure water vapor is passed through the first chamber and the second chamber 110, 120 of the hollow fiber membrane filter, thereby sterilizing the first chamber and the second chamber. As the ultrapure water vapor passes through the first and second chambers, it cools, causing a portion of the ultrapure water vapor to condense. The mixture of ultrapure water vapor and condensed water is referred to as condensate in the technical process and is discharged from the second chamber and the first chamber via the fluid inlets 102b, 103b and the connection devices 150A and 150B. In one embodiment, the duration of the sterilization step is 900 s. Depending on the design of the hollow fiber membrane filter, a different duration of the sterilization step may be provided, e.g., 200 to 1400 s, or 400 to 1100 s, or 400 to 800 s.

[0024] In a further embodiment, the method according to the invention is characterized in that the introduction, in particular passage of sterile compressed air into / through the second space and the introduction, in particular passage of ultrapure water into / through the first space of the hollow fiber membrane filter during the leakage test are carried out according to the countercurrent principle.

[0025] In a further embodiment, the process according to the invention is characterized in that the temperature of the water which is passed through the first and the second space of the hollow fiber membrane filter is 50 to 120°C or 50 to 95°C or 60 to 90°C or 65 to 90°C or 70 to 90°C.

[0026] In a further embodiment, the method according to the invention is characterized in that the sterilizing fluid is steam, in particular ultrapure steam at a temperature of 105 to 150°C, which is introduced into the first and second chambers of the hollow-fiber membrane filter at a pressure of 1.1 to 3 bar. In particular, pressures of 1.1 to 2.5 bar, or 1.1 to 2 bar, or 1.1 to 1.8 bar, or 1.2 to 1.6 bar can also be provided for the sterilization step. Alternative temperatures of the ultrapure steam can be between 110 to 140°C or between 115 and 130°C.

[0027] In a further embodiment, the method according to the invention is characterized in that between the leakage test and the sterilization step, a blow-out step with sterile compressed air is carried out, wherein the first and the second space of the hollow fiber membrane filter are blown out with sterile compressed air.

[0028] Fig. 4 shows a schematic representation of this blow-out step. The arrangement of the hollow fiber membrane filter, the connection devices 150A, 150B, 150C, 150D in conjunction with the sterilization device (not shown in Fig. 4) is the same as in Figs. 1 to 3. Fig. 4 schematically shows that sterile compressed air is introduced into and passed through the first and second chambers 110, 120 of the hollow fiber membrane filter via the connection devices 150C and 150D and the fluid inlets 103a, 102a. The sterile compressed air is discharged as exhaust air from the first and second chambers 110, 120 of the hollow fiber membrane filter via the connections 103b and 102b and the respective connection devices 150B and 150A. The pressures of the sterile compressed air flowing into the first and second chambers 110, 120 are essentially the same, e.g. between 1 and 2 bar.The blow-out step expels any remaining water from the leak test from the first chamber 110 of the hollow-fiber membrane filter. However, the pores of the membrane wall of the hollow-fiber membranes preferably remain filled with water. The filter is thus advantageously conditioned for the subsequent steam sterilization step. Depending on the design of the hollow-fiber membrane filter, the blow-out step can be performed for a duration of 30 to 90 seconds, 40 to 80 seconds, or 50 to 70 seconds.

[0029] In a further embodiment, the method according to the invention is characterized in that, prior to the leakage test, a steam injection step is carried out, in which water vapor is introduced, in particular passed through, the first and second chambers of the hollow fiber membrane filter. The steam injection step is carried out according to the schematic representation in Fig. 3. In the steam injection step, ultrapure water vapor is introduced via the connection devices 150C and 150D and the fluid inlets 103a and 102a into the first chamber 110 and the second chamber 120 of the hollow fiber membrane filter. The ultrapure water vapor is provided via the sterilization device and, according to the diagram shown, has Embodiment a temperature of 123°C and a pressure of 1.3 bar. Depending on the design of the hollow fiber membrane filter, other pressures and temperatures can also be provided. In particular, pressures of 1.1 to 3 bar or 1.1 to 2.5 bar or 1.1 to 2 bar or 1.1 to 1.8 bar or 1.2 to 1.6 bar can also be provided for the steam boost step. Preferably, the pressure of the ultrapure water vapor in the first and second chambers of the hollow fiber membrane filter in the steam boost step is essentially the same. Alternative temperatures of the ultrapure water vapor can be between 50 to 150°C or 105 to 150°C or between 110 to 140°C or between 115 to 130°C. The ultrapure water vapor is passed through the first chamber and the second chamber 110, 120 of the hollow fiber membrane filter, and the first chamber and the second chamber are thereby conditioned.As the ultrapure water vapor passes through the first and second chambers, the ultrapure water vapor cools, causing a portion of the ultrapure water vapor to condense. The mixture of ultrapure water vapor and condensed water is referred to as condensate in the technical process and is discharged from the second chamber and the first chamber via the fluid inlets 102b, 103b and the connection devices 150A and 150B. In one embodiment, the duration of the steam burst step is 90 s. Depending on the design of the hollow fiber membrane filter, a different duration of the steam burst step can be provided, e.g., 40 to 140 s, 50 to 110 s, or 60 to 100 s. The steam burst step preconditions the hollow fiber membrane filter in terms of temperature and pressure for the subsequent sterilization step. This allows potential leaks to be more accurately detected in the subsequent leak test before the sterilization step.

[0030] In the embodiment described above, the method according to the invention is further characterized in that the introduction, in particular the passage of water vapor in the steam jet step into the first and second chambers of the hollow fiber membrane filter takes place according to the cocurrent principle.

[0031] In a further embodiment, the method according to the invention is characterized in that the water vapor in the first and second chambers of the hollow fiber membrane filter has substantially the same pressure, or that the water vapor in the first chamber has a higher pressure than the water vapor in the second chamber. The pressures in the first and second chambers can be varied during the steam injection step. In particular, a higher pressure in the first chamber can result in a transmembrane transfer of the ultrapure water vapor from the first chamber to the second chamber. This step can, for example, loosen blockages in the pores of the membrane wall and loosen the hollow fiber membranes in the hollow fiber membrane filter, thus ultimately increasing the separation performance of the hollow fiber membrane filter in filtration applications, i.e. the so-called clearance. It can therefore be provided that the pressure in the first chamber is 1.5 bar or 1.3 bar or 0.8 bar greater than the pressure in the second chamber, whereby the pressure in the second chamber can then be 0.3 bar or 1.3 bar or 1.5 bar.

[0032] In a further embodiment of the method according to the invention, the rinsing step is performed between the steam jet step and the leak test. This advantageously allows adhesions and particles released by the steam jet step to be removed from the hollow fiber membrane filter before the leak test and sterilization steps.

[0033] In a further embodiment of the method according to the invention, it is provided that a first blow-out step takes place before the steam jet step, in which the first space and the second space of the hollow fiber membrane filter are blown out with sterile compressed air.

[0034] The first blow-out step is carried out analogously to the blow-out step schematically shown in Fig. 4. The arrangement of the hollow fiber membrane filter, the connection devices 150A, 150B, 150C, 150D in conjunction with the sterilization device (not shown in Fig. 4) is the same as in Figs. 1 to 3. Fig. 4 schematically shows that sterile compressed air is introduced into and passed through the second and first chambers 120, 110 of the hollow fiber membrane filter via the connection devices 150D and 150C and the fluid inlets 102a, 103a. The sterile compressed air is discharged as exhaust air from the first and second chambers 110, 120 of the hollow fiber membrane filter via the connections 103b and 102b and the respective connection devices 150B and 150A. The pressures of the sterile compressed air flowing into the first and second chambers 110, 120 are essentially the same, e.g., between 1 and 2 bar. In the first blow-out step, the hollow fiber membrane filter is pre-dried for the subsequent steam jet step. Depending on the design of the hollow fiber membrane filter, the first blow-out step can be carried out for a duration of 30 to 90 s, 40 to 80 s, or 50 to 70 s.

[0035] In a further embodiment, the method according to the invention is characterized in that the sterilization step is followed by a drying step in which sterile compressed air is passed through the first chamber and the second chamber of the hollow-fiber membrane filter. Technically, the drying step is carried out analogously to one of the previously described blow-out steps. Depending on the design of the hollow-fiber membrane filter, however, the drying step is carried out for a duration of 900 to 1800 s, 1100 to 1600 s, 1200 to 1500 s, or 1250 to 1400 s.

[0036] After the drying step, the hollow fiber membrane filter is ready for use. The fluid inlets 102a, 102b, 103a, and 103b are sealed with appropriate caps to prevent germs from entering the filter. The fluid inlets are preferably sealed under sterile conditions in the connection devices 150A, 150B, 150C, and 150D.

[0037] In a further embodiment, the process according to the invention is characterized in that the hollow fiber membranes of the hollow fiber membrane filter comprise polysulfone and polyvinylpyrrolidone or consist of polysulfone and polyvinylpyrrolidone.

[0038] In a further preferred embodiment, the hollow-fiber membranes are produced using the following method: A spinning solution consisting of 16 parts by weight of polysulfone (P3500 from Solvay), 4.4 parts by weight of polyvinylpyrrolidone (K82-86 from Ashland), and 79.6 parts by weight of DMAC is processed into a homogeneous spinning dope by stirring, heating to 60°C, and degassing. The spinning dope is extruded into a spinning thread through an annular die containing a centrally directed precipitant consisting of 35% DMAC and 65% water. The precipitant is guided inside the hollow spinning thread. The temperature of the annular die is 70°C. The extruded spinning thread is passed through a precipitation chamber whose atmosphere has a relative humidity of 100%. The height of the felling gap is 200mm and a dwell time of 0.4 s is set in the felling gap. The spinning thread is immersed in the water-based and The hollow fiber membrane is then passed through a rinsing bath heated to 80°C and precipitated into a hollow fiber membrane. The hollow fiber membrane is then passed through rinsing baths heated to a temperature of 75°C to 90°C. The hollow fiber membrane then undergoes a drying process at a temperature between 100°C and 150°C.

[0039] To construct a hollow fiber membrane filter, the resulting hollow fiber membrane is then taken up from a reel and assembled into a sheet of threads. Hollow fiber membrane bundles are then produced from the reeled sheet of threads and used in the construction of the hollow fiber membrane filters.

Claims

CLAIMS 1. A method for sterilizing a hollow fiber membrane filter comprising a plurality of hollow fiber membranes sealed at the ends in the housing of the hollow fiber membrane filter such that a first space is created that encompasses the interior of the hollow fiber membranes, and a second space is created that encompasses a space between the hollow fiber membranes, wherein the hollow fiber membrane filter has at least two fluid inlets connected to the first space and at least two fluid inlets connected to the second space, and wherein the fluid inlets are prepared to be connected to a sterilization device, comprising at least the steps of: a) rinsing the hollow fiber membrane filter with a fluid, in particular water, wherein the rinsing fluid is passed through the first and second spaces of the hollow fiber membrane filter via a selection of the fluid inlets, b) performing a leakage test,c) Sterilizing the hollow fiber membrane filter with a sterilizing fluid, in particular heated water or steam, wherein the sterilizing fluid is passed through the first and second spaces of the hollow fiber membrane filter via a selection of fluid inlets, characterized in that the leakage test is carried out before the sterilization step.

2. Method according to claim 1, characterized in that in the leakage test sterile compressed air is passed into the second chamber of the hollow fiber membrane filter, in particular is passed through, and high-purity water is passed into the first chamber of the hollow fiber membrane filter, in particular is passed through, and the pressure in the second chamber is higher than in the first chamber.

3. Method according to claim 2, characterized in that the introduction, in particular passing through of sterile compressed air into the second chamber and the introduction, in particular passing through of ultrapure water into the first chamber of the hollow fiber membrane filter take place according to the countercurrent principle.

4. Method according to one of the preceding claims, characterized in that the temperature of the water passed through the first and second chambers of the hollow fiber membrane filter is 50 to 120°C.

5. Method according to one of the preceding claims, characterized in that the sterilizing fluid is steam at a temperature of 105 to 150°C, which is introduced into the first and second chambers of the hollow fiber membrane filter at a pressure of 1.1 to 3 bar.

6. Method according to one of the preceding claims, characterized in that between the leakage test and the sterilization step, a blow-out step with sterile compressed air is carried out, wherein the first and second spaces of the hollow fiber membrane filter are blown out with sterile compressed air.

7. Method according to one of the preceding claims, characterized in that before the leakage test, a steam injection step is carried out in which water vapor is passed, in particular passed through, into the first and second chambers of the hollow fiber membrane filter.

8. Method according to claim 7, characterized in that the introduction, in particular the passing through of water vapor into the first and second chambers of the hollow fiber membrane filter takes place according to the cocurrent principle.

9. A process according to claim 7 or 8, characterized in that the steam has a temperature of 100 to 150 °C and a pressure of 1.1 to 3 bar.

10. The method according to claim 7 to 9, characterized in that the water vapor in the first and second chambers of the hollow fiber membrane filter has substantially the same pressure, or that the water vapor in the first chamber has a higher pressure than the water vapor in the second chamber.

11. Method according to one of claims 7 to 10, characterized in that the rinsing step takes place between the steam jet step and the leakage test before sterilization.

12. Method according to one of claims 7 to 11, characterized in that before the steam jet step a first blowing-out step takes place in which the first space and the second space of the hollow fiber membrane filter are blown out with sterile compressed air.

13. Method according to one of the preceding claims, characterized in that the sterilization step is followed by a drying step in which sterile compressed air is passed through the first space and the second space of the hollow fiber membrane filter.

14. Process according to one of the preceding claims, characterized in that the hollow fiber membranes comprise polysulfone and polyvinylpyrrolidone or consist of polysulfone and polyvinylpyrrolidone.

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