WO1998035749A1

WO1998035749A1 - Cross-filter apparatus

Info

Publication number: WO1998035749A1
Application number: PCT/JP1998/000601
Authority: WO
Inventors: Tatsuya Shimoda
Original assignee: Nihon Millipore Kabushiki Kaisha
Priority date: 1997-02-14
Filing date: 1998-02-13
Publication date: 1998-08-20
Also published as: JPH10225628A

Abstract

A cross-filter apparatus for making it easy to confirm filtering performance after a filtration operation of a sterilized filter disc, filter cartridge or disposable filter, and to avoid contamination. The cross-filter apparatus comprises a filter having a solid/liquid mixture feed piping and a liquid recovery piping connected to the upstream and downstream sides of a filter assembly (37) through valves (11 and 13), respectively, a filter membrane integrity tester having a pressure test fluid feed piping and a test fluid discharge piping connected to the upstream and downstream sides of the filter assembly (37) through valves (1 and 3), respectively, and a sterilizer having a reagent feed piping for sterilization and a reagent discharge piping for sterilization connected to the upstream and downstream sides of the filter assembly (37) through valves (21 and 23), respectively, particularly when a sterilization operation is essentially necessary. Each of these units uses in common the filter assembly and is cross-connected.

Description

Description-Cross-filtration equipment Technical field

The present invention relates to a filter device provided with a filter assembly for separating solids from a solid-fluid mixture containing fine solids, and an integrity test device for testing the physical properties and performance of the filter membrane. Regarding the cross-connected devices, in another embodiment, the sterilization device sharing this filter assembly is also related to the cross-connected devices, and the respective devices are opened and closed by opening and closing a predetermined valve disposed in place. The present invention relates to a cross-filtration apparatus characterized by being capable of performing a single function operation, that is, a filtration operation, a filter membrane integrity test operation of a filter assembly, and a sterilization operation. Conventional technology

Conventionally, before applying a filter disc, a filter cartridge, or a disposable filter to a filtration device, a filter membrane integrity test was performed on the filter element, a filter element, to confirm the specified filtration performance (Nippon Kogyo As described in the standard JISK 382, a test to confirm that the filter has no physical defect and has a rated removal performance) has been performed to confirm the integrity of the filter membrane using a dedicated device. . In other words, the first confirmation, which should be called confirmation of the pre-filtration performance of the filter membrane, has been performed to ensure an appropriate filtration operation. Next, after applying the first confirmed filter membrane to the filtration device and performing a predetermined filtration operation to collect the fluid, it is again confirmed that the immediately preceding filtration operation was performed under the predetermined performance of the filter membrane. Therefore, the integrity of the filter membrane has been confirmed using a dedicated device for the filter membrane integrity test. That is, a second confirmation, which should be called confirmation of performance after filtration, has been made. Confirmation of filter performance before and after the operation of these filtration devices is indispensable to give certainty to the filtration operation, and has been evaluated as such. Problems of the Invention

By the way, during the first check of the filter disk or the filter cartridge or the disposable filter, and before removing it from the dedicated device for integrity test and incorporating it into the filtration device, these are the atmosphere in the integrity test and the surrounding area. It was unavoidable to be contaminated by contact with the environment, for example, by contact with airborne dust and bacteria. Therefore, when such contamination must be removed, a step of providing an operation for the purpose of "cleaning, sterilizing, sterilizing or aseptic" (hereinafter simply abbreviated as "sterilization") of the filtration device is particularly necessary in a field where microbial contamination is rejected. It has been taken as an integral part. That is, after the filter disk, filter cartridge, or disposable filter, which has been subjected to the first confirmation described above, is incorporated into the filtration device, `` pure water, hot water, steam, or pure water is used as pre-filtration treatment for sterilizing the filtration device. Sterilization using a reagent gas suitable for sterilization (eg, dilute ethylene oxide gas) or liquid (eg, alcohol) ”(hereinafter simply abbreviated as“ reagent for sterilization ”) is applied. As a result, the filtration operation is performed under sterile conditions. It is now possible to implement.

However, such a pre-filtration treatment for sterilization sometimes causes the filter membrane to be damaged and fail to maintain the predetermined filtration performance, and if the filtration operation is continued without being detected, the filtration operation may be stopped. For the first time in the above-mentioned second confirmation, it was found that the filter membrane subjected to the filtration operation did not satisfy the predetermined performance. At that time, the recovered fluid did not achieve the predetermined solid separation, and required a re-filtration operation, which necessitated complicated measures and appropriate measures were desired. In particular, when dealing with a solid-fluid mixture that tends to change over time, it has naturally been desired to avoid such repetition of the filtration operation.

Therefore, if a filter membrane integrity test, which can be called an intermediate check, is introduced to check the performance of the filter membrane after the sterilization operation before filtration, and then the filter operation is started, the filter membrane may be damaged during filtration. Even if it is unavoidable that it is not possible to cope with the problem, it will be possible to shift to the appropriate filtration operation appropriately except for this case.

However, the filter disc or the filter kept sterile in the filter device It is difficult to avoid re-contamination of the filter membrane by removing the filter or disposable filter from the filtration device and removing it from the filtration device, and then removing the disposable filter for the integrity test of the filter membrane integrity test. In order to avoid this, it is required that the filter, filter membrane integrity test device, filter disk, finole cartridge, and also the surrounding environment handling the disposable filter be free of contamination. However, maintaining all of these devices in a sterile condition, including the surrounding environment, requires major special equipment improvements, so sterile filter discs or filter cartridges are required.

— The task was to develop a device that could easily test the integrity of the filter membrane immediately before the filter function, while avoiding re-contamination of the trige or even the disposable filter. Summary of the Invention

Based on the above background, in addition to the damage of the filter membrane during the sterilization operation, remove the filter disk, filter force cartridge or disposable filter that has been subjected to the first confirmation from the dedicated filter membrane integrity test device. In rare cases, when these components are removed and attached to a filtration device, they may be properly set or damaged, and the process may shift to sterilization or filtration without knowing this. However, in some cases, it was not possible to achieve the required filtration, and in some cases, valuable solid / fluid mixtures could be lost outside the system. .

As a result, the various fluids used for the filter membrane integrity test can be easily supplied in a sterilized state, and once the filter desk, filter cartridge, or disposable filter is attached to the filtration device, do not remove it from the filtration device until the filtration is completed. And at least pressurized through a valve upstream and downstream of the filter assembly, with a filter connected to the solid / fluid mixture supply pipe and the fluid recovery pipe at least upstream and downstream of the filter assembly. The present inventor has found a cross-filtration device comprising a filter membrane integrity test device connected to a test fluid supply pipe and a test fluid discharge pipe, and has been able to solve the above problems. Especially sterilization operation Indispensable, it is necessary to find a cross filtration device that includes at least a sterilization reagent supply pipe and a sterilization reagent discharge pipe connected via valves upstream and downstream of the filter assembly. Reached.

As in the prior art, the filtration device, which is one of the constitutions of the present invention, naturally has a filter assembly and a solid fluid mixture as a filtration material is supplied from the upstream of the filter assembly through a solid / fluid mixture supply pipe, and is filtered. The solids are trapped on the filter membrane in the filter assembly, and the fluid passes through the filter membrane and is discharged and collected from the downstream of the filter assembly through the fluid collection pipe.

However, in order to operate and operate the filter membrane integrity test device, which is the crossed device described later, alone, the filter device needs to be cut off during the test. It is required that the fluid recovery pipe be connected to the filter assembly via a valve. In addition, as long as the above-mentioned purpose of the cross-filtration device is achieved, if necessary, further upstream and downstream of the filter assembly, various ancillary equipment for filtration operation, such as installation of exhaust valves and drain valves, temperature, pressure, flow rate, etc. May be attached.

A filter membrane integrity test apparatus, which is one of the configurations of the present invention, shares the same filter assembly of the above-described filter apparatus, and a pressurized test fluid is supplied to the upstream of the filter assembly via a pressurized test fluid supply pipe, and downstream of the filter assembly. The test fluid is discharged through the connected test fluid discharge pipe.

However, in order to operate and operate the above-mentioned cross-linked filtration device alone, the filter membrane integrity test device must be cut off during the filtration. The fluid discharge pipe needs to be connected to the filter assembly via a valve. In addition, as long as the above-mentioned purpose of the cross-filtration device is achieved, as necessary, upstream and downstream of the filter assembly, various auxiliary equipment for filter membrane integrity testing, for example, installation and temperature of exhaust valves and drain valves, etc. , Pressure, flow rate and other measuring elements may be attached.

The sterilization apparatus, which is one of the constitutions of the present invention, shares the same filter assembly of the above-mentioned filtration apparatus, and the sterilizing reagent flows upstream of the filter assembly via the sterilizing reagent supply pipe. The apparatus is configured to be supplied and to discharge the sterilizing reagent via a sterilizing reagent discharging pipe connected downstream thereof.

However, in order to function and operate the above-mentioned crossed devices, the filtration device or the filter membrane integrity test device alone, the sterilizer must be trimmed during its filtration or test. The sterilizing reagent supply pipe and the sterilizing reagent discharge pipe need to be connected to the filter assembly via a valve. In addition, as long as the above-mentioned purpose of the cross-filtration device is achieved, various ancillary equipment for sterilization operation such as installation of exhaust valves and drain valves, temperature, pressure, flow rate, etc. A measuring element may be attached.

Thus, by closing the valves of the filter membrane integrity test device and the sterilization device upstream and downstream of the filter assembly, the filtration device can be cut off to allow the filtration device to function properly, and the filter membrane integrity test can be performed. In the test operation, the sterilization device and the filtration device upstream and downstream of the filter assembly are closed by closing the respective valves to allow the filter membrane integrity test device to function properly and sterilization. In operation, by closing the respective valves of the filtration device and the filter membrane integrity test device, these devices could be cut off and the sterilizer could function properly. In other words, the filter membrane integrity test of the intermediate confirmation was performed only by closing the valve, and the sterilized state after the sterilization treatment could be easily maintained.

The piping and valves upstream and downstream of the filter assembly provided for each device may be shared as much as possible, or may be replaced with a three-way valve or other means. Other equipment for integrity testing, excluding the filter assembly, if the combination of devices is mentioned, will be arranged in series upstream and downstream of the filter assembly of the filtration device, i.e. both non-intersecting It does not imply a combination of devices.

Here, a filter assembly is a filter element that cannot be directly applied to a filtration device as a filter membrane (microfiltration membrane). Therefore, the filter assembly is attached to a housing or holder having various supports, fasteners, and the like as necessary. Refers to the module Specifically, a disposable filter in which a filter membrane and a housing are integrated into one, and a disposable filter, and a filter element in the form of a pleated or cylindrical filter element designed to be exchangeable. This is a generic term for a cartridge filter containing a cartridge in a cartridge or a holder filter containing a filter disk, which is a sheet-like filter element, in a holder. It is determined according to 32. For example, in FIGS. 1 to 4, in the filter assembly 37, the filter membrane 35 is housed in a sealed nozzle 36, and the filter membrane 35 separates the upstream side and the downstream side. I have. The liquid or gas to be filtered is introduced into the upstream side through valve 1 or valve 5, and the liquid or gas that has passed through filter membrane 35 is passed through valve 3 or as a purified stream through valve 3 and then through valve 8. It is led to the place of.

In addition, other devices connected to the above-mentioned filter assembly and the filter membrane integrity test device that is cut off include “microfiltration membrane element and module bubble point test device”, “microfiltration membrane element and diffusion of module”. Flow rate test apparatus "and" intrusion (intrusion) liquid flow rate test apparatus for microfiltration membrane elements and modules ", which are used to determine the nominal performance of the filter membrane derived from the maximum pore porosity of the filter membrane. This device is equipped with measurement means for bubble generation observation, pressure change measurement, and fluid measurement.

In other words, bubble bubble test of the microfiltration membrane element and module is to wet the microfiltration membrane element and the filter membrane of the module sufficiently with an appropriate liquid, and then pressurize it with an appropriate gas and pressurize the micropores of the filter membrane. This is a test to confirm the integrity of the filter membrane by measuring the differential pressure when air bubbles are released from the filter. The equipment used for this is a microfiltration membrane element and a bubble point test apparatus for the module. Figure 1 shows the test gas source 3 1, gas pressure regulator 32, thermometer 33, pressure gauge 34, filter assembly 37, piping with valves 2, 4, 6, 7 and graduated cylinder 3 An example of an apparatus configuration including 9 and the like is shown. As is evident from the above, the pressurized test fluid in this test is a gas, and usually air or nitrogen is used, and piping with valves 2, 6, and 7 is added upstream of the filter assembly 37 for the supply. It is a pressure test fluid supply pipe. On the other hand, the test fluid discharge was This means that these gases, that is, the normal air and nitrogen described above, are released outside the system as bubbles in the liquid of the graduated cylinder 39 through the micropores of the filter cylinder. A pipe 38 provided with a valve 3 and a pressure gauge 34 downstream of 37 is a fluid outflow pipe. Further details are disclosed in Japanese Industrial Standard JISK 3 832.

In the diffusion flow rate test of the microfiltration element and the module, the precise filtration membrane element and the filter membrane of the module were sufficiently wetted with an appropriate liquid, and an appropriate pressure difference equal to or less than the bubble point was applied with an appropriate gas. This is a test to check the integrity of the filter membrane by measuring the flow rate of gas permeating to the secondary side by diffusion in an appropriate method, and the equipment used for this is a microfiltration membrane element and a module. Is a diffusion flow rate test device. Figure 2 shows an example of the device configuration. As is clear from the above, the pressurized test fluid in this test is a gas, and usually air or nitrogen is used, and piping with valves 2, 6, and 7 is added upstream of the filter assembly 37 to supply it. It is a pressure test fluid supply pipe. The specific configuration of the pressurized test fluid supply pipe is the same as that shown in Fig. 1, so please refer to the description. On the other hand, test fluid discharge refers to the phenomenon of dissolving from the pressurized side into the liquid in the micropores of the filter membrane 35 and dissipating on the low pressure side to generate a steady gas flow, and is measured both upstream and downstream of the filter assembly. It is possible, and the pipe with valve 3, pressure gauge 34, and flower 40 downstream of the filter assembly for its discharge is the fluid outflow pipe. Further details are disclosed in Japanese Industrial Standard JISK 3833.

In addition, in the microfiltration membrane element and the infiltration liquid flow rate test of the module, water or an aqueous solution of a composition range that does not wet the pressure is supplied to the completely dried microfiltration membrane element and the hydrophobic filter membrane of the module. By injecting water or an aqueous solution in a non-wetting composition range in contact with the pores of the filter membrane against the surface tension, and measuring the pressure when observing a steady flow rate of the detected water or an aqueous solution in a non-wetting composition range, This is a test to confirm the integrity of the filter membrane, and the equipment used for this is a microfiltration membrane element and a liquid intrusion test equipment for the module. Figure 3 shows an example of the device configuration. As evident from the above, the pressurized test fluid in this test is a liquid, and water or various aqueous solutions having a composition range that does not wet the filter membrane are used. Fluid, mainly gas, that transmits pressure through the permeable membrane is employed, and a pipe provided with a valve upstream of the filter assembly for supplying them is a pressurized test fluid supply pipe. The configuration of the pressurized test fluid supply pipe is the same as that in FIG. 1, so refer to the above description. In this example, the flow meter 41 is used on the pressurized test fluid supply pipe side, but may be used on the discharge side. On the other hand, the test fluid is discharged downstream of the stationary filter membrane that shows water only in contact with the micropores of the filter membrane or an aqueous solution with a non-wetting composition range, penetrating only after reaching the constant pressure and reaching a certain pressure. The outflow means a pipe provided with a valve 3 and a pressure gauge 34 downstream of the filter assembly for discharging the fluid. Further details are described in the examples.

Each test of the above-mentioned microfiltration membrane element and module can be variously modified within the range not deviating from each principle as already explained in the Annex of Japanese Industrial Standard JIS. In addition to measuring the intruding liquid flow upstream of the filter membrane as well as measuring the intruding liquid flow downstream of the filter, we apply the principle widely and wet the hydrophilic filter membrane. It is also possible to apply direct pressurization with an inert gas for the purpose of infiltrating various organic solvents or their mixtures as intrusion liquids, and furthermore, for the sake of safety. Includes two filtration units that are installed in parallel with two jiLh assemblies and switched when the differential pressure across the filter increases. , But also includes cross filtration device having two or more crossing number of crossed sterile test apparatus and fill evening membrane integrity test apparatus or filter membrane integrity test apparatus accordingly. In this case, the integrity test of the filter membrane or the sterilization process after the complete test can be performed in parallel with the filtration operation, and it is possible to reduce the waiting time between switching the filter assembly and the subsequent filtration operation. It is preferable from the viewpoint of increasing the efficiency of the operation. Furthermore, some integrity test equipment can be dedicated to integrity test equipment.

In addition, the filtration device that crosses the integrity test device according to the present invention will lose valuable solids and fluid mixture, which is a precious filtration material, if the operation procedures and various controls of the related valves are not performed according to the manual. , Which is made under automatic control preferable. In particular, according to the present invention, there is also a feature that the filter can intersect the filtering device as compactly as possible without considering the versatility that the dedicated device for integrity test should have. Further, as an operation procedure of the filtration device of the present invention, it is possible to omit the integrity test for the first confirmation and to simplify the filtration operation such as starting the sterilization process. BRIEF DESCRIPTION OF THE FIGURES

Figure 1 is a diagram of a bubble filtration test device for microfiltration membrane elements and modules.

FIG. 2 is a diagram of a diffusion flow rate test device for a microfiltration membrane element and a module. FIG. 3 is a diagram of an infiltration liquid flow rate test device for a microfiltration membrane element and a module. FIG. 4 is a diagram of a cross filtration device of the present invention. Embodiment of the invention

The present invention is constructed and implemented by cross-connecting the filter assembly of the filter assembly with the filter membrane integrity test device of the filter assembly or further cross-connecting the sterilization device of the filter assembly. The valve is arranged upstream and downstream of the filter assembly so that each function is performed separately from other functions. Note that the present invention essentially requires a filter device having a cross connection of a filter membrane integrity test device, and a cross-connection of a sterilization device is a more preferable embodiment.

FIG. 4 shows an example of a cross filtration device in which the filtration device, the intruding liquid flow rate test device, and the sterilization device share the filter assembly 37, that is, are cross-connected, according to the present invention. In other words, the filtration device is connected to each equipment including the pipes indicated by dotted lines with valves 11 and 13, and the microfiltration membrane element and the infiltration liquid flow rate test device for the module have solid lines with valves 1 and 13. Each equipment is connected and configured by the piping indicated by, and furthermore, the sterilization equipment is connected and configured by the dashed-dotted pipe having valves 21 and 23, and the filter assembly 37 is shared by all equipment The cross-filtration apparatus described is shown. The filtration device of this example is a device for producing sterilized air for pumping an injection drug solution or the like. The filter membrane 35 in the airtight case 36 of the filter assembly 37 was provided with a fluorine-based hydrophobic membrane having a nominal cylindrical pore diameter of 0.2 μιη. The infiltration liquid flow rate test device for the filter membrane 35 gradually raises the pressure of the intrusion liquid pure water with dry nitrogen from the gas cylinder 31 and presses it into the pores of the filter membrane 35. A pure water flow rate of 201 / min was measured, and a differential pressure of 144 kPa at that time was read. Further, the sterilizing device of the filter assembly 37 which is cross-connected is a device for heat sterilization by steam supply. Hereinafter, a procedure for using the cross filtration device of the present embodiment will be described in detail.

First, a filter assembly 37 having a filter membrane 35 is attached to a cross filtration device and operated as an intrusion liquid flow test device. That is, the dry nitrogen gas 31 is allowed to flow from the gas cylinder to the filter assembly 37 unless it is known that the filter membrane is sufficiently dry. At this time, the valves 7, 2, and 3 are opened, the valve 6 is controlled by the controller 32, and a predetermined amount is flowed to dry. It is effective to keep other valves closed but occasionally open and close them for a short period of time as necessary to remove water and other dead volume (deadspace). In particular, the presence of a liquid that dissolves in water and wets the fluorine-based hydrophobic membrane does not provide accurate test results.Thus, it is necessary to analyze the water and other components in downstream nitrogen to ensure thorough removal. . Then, valves 2 and 3 are closed, valves 1 and 4 are opened, and pure water, which is the intruding liquid, is released from valve 1 through the nominal cylinder bore, and the intrusion pressure (P t) calculated by the following formula, or the nominal intrusion pressure 2 7 It is supplied from the upstream side of the filter assembly 37 under a pressure of less than 0 kPa, and the upstream filter membrane 35 is filled so as to be submerged so as not to come into direct contact with nitrogen or other gas.

(However, δ is the surface tension, Θ is the wetting angle, 90. <0, d is the maximum value of the assumed cylindrical hole.)

That is, it can be achieved by allowing pure water to flow out sufficiently from the valve 4.

Valves 1 and 4 are closed, valve 3 is opened, and the valve is operated in the same manner as the drying operation, and the pressure of the supplied nitrogen is gradually increased via valve 6. During this time, the pseudo flow rate is occasionally detected by the flow meter 32, and it is observed that the flow stops. However, the flow rate was not steady, and the flow rate was different from that at the first steady flow after pressure reduction. After the completion of the integrity test, steam of 220 kPa is supplied from the valve 21 to sterilize not only the filter membrane 35 but also the filter assembly 37 or the piping around it. Valves 23 are steam drain valves. Normally, the other valves should be closed, but pipes where steam may condense and accumulate water may be opened occasionally for closed pipes.If there are no valves, joints etc. may be loosened for a while to condense water. It is important to ensure that steam is sterilized by discharging steam. The steam supply pipes and equipment were equipped with heat insulating material and the sterilization operation was completed in a short time. After the sterilization operation is completed, the infiltration liquid flow test is performed again to confirm that there is no leak in the filter filter as well as in the cross filtration device by sterilization and other related operations, but the procedure is the same as described above. However, it is essential to pay attention to the need for a filter membrane. If the same intrusion pressure as in the first confirmation is measured, the operation shifts to the filtration operation. The valves 11 and 13 were opened, the other valves were closed, the solids were filtered off, and purified air could be produced via valve 13.

The cross-filtration device according to the present invention requires only one filter assembly work from the initial filter membrane integrity test to the end of filtration, so that various fluids and solid-fluid mixture systems associated with installation failures are required. The possibility of leaks can be dealt with by the first filter membrane integrity test, and each subsequent operation can be performed simply by opening and closing the valves installed upstream and downstream of the filter assembly. It became a thing. That is, the integrity test of the filter membrane before and after the sterilization operation can be performed simply by opening and closing the valve, and naturally, the leakage of the sterilization reagent can be avoided. It was possible to avoid this, and the filtration operation itself could be performed after confirming the performance of the filter membrane after sterilization in the integrity test. Also, by placing multiple filter assemblies in parallel on the filtration device, it is possible to perform a filter membrane integrity test and sterilization operation of the filter assembly before using it for filtration during the filtration operation, so a filtration operation is necessary. Therefore, the filter assembly can be switched and switched smoothly and efficiently. In addition, the parallel arrangement described above allows a part to be used as a single filter membrane integrity test device. It became possible to use it.

Claims

The scope of the claims -

1. A filtration device having at least a solid fluid mixture supply pipe and a fluid recovery pipe connected upstream and downstream of the filter assembly via valves, respectively, and at least a pressurized test fluid supply via valves upstream and downstream of the filter assembly, respectively. Cross-filtration device consisting of a pipe membrane and a filter membrane integrity tester connected to the discharge pipe

2. The cross filtration device according to claim 1, wherein a sterilization device having at least a sterilization reagent supply pipe and a sterilization reagent discharge pipe connected via a valve upstream and downstream of the filter assembly is provided.

3. The cross filtration device according to claim 1, wherein the filter membrane integrity test device is a microfiltration membrane element and a module bubble point test device.

4. The cross filtration device according to claim 1, wherein the filter membrane integrity test device is a microfiltration membrane element and a device for measuring the diffusion flow rate of a module.

5. The cross-filtration device according to claim 1, wherein the filter membrane integrity test device is a microfiltration membrane element and a device for infiltrating liquid flow of a module.