Integrity test of double filter capsules
Patent Information
- Application Number
- CN202180093436.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Priority Date
- 2020-12-23
- Filing Date
- 2021-12-22
- Publication Date
- 2026-10-09
- Estimated Expiration
- 2041-12-22
Smart Images
Figure CN116868044B_ABST
Abstract
Description
[0001] This invention relates to inspecting the integrity, particularly of sterile dual-filter capsules, especially the sealing or reliability of their ability to retain the filtered material. The invention specifically incorporates a "pre-use-post-sterilization integrity test," i.e., used before using sterile dual-filter capsules during filtration, wherein the integrity, sealing, or reliability of the ability to retain the material to be filtered from a filter capsule equipped with (at least) two integrated filters within a single or combined housing can be checked without compromising the sterility of the filter capsules or the structure in which the filter capsules are integrated for the application.
[0002] In other words, the present invention relates to integrity testing of dual assemblies of (at least) two filters integrated in a common housing, wherein at least one filter is preferably a sterile filter. In this document, integrity testing may correspond to bubble point testing, diffusion testing, and / or pressure holding testing, or at least be similar to or include one or more of these tests.
[0003] In pharmaceutical processes, such as the production of antibodies or drugs, aseptic filtration is used as a standard procedure. In many cases, this type of sterilization is the only option for the production of active ingredients based on novel biotechnology involving complex (biological) molecules, as other methods such as heating or exposure to gamma rays can damage, denature, or destroy the molecules. To improve sterilization safety and control over process management, there is a growing desire to use at least two cascaded filtration units in filtration assemblies as redundant or complementary units. In single-use configurations, for example, two filter capsules connected by tubing are arranged one after the other.
[0004] In particular, Figure 7 An exemplary arrangement of a conventional complex dual-filter system 100 is shown. A first filter 110 is fluidly connected to a second filter 120 via a hose connection 130. The first filter 110 can be supplied with the medium to be filtered via a line 150 at its inlet. After filtration through the first filter 110, the medium can be supplied to the second filter 120 via the hose connection 130 and, through the second filter, then discharged via another line 160 downstream of the outlet of the second filter 120, particularly as a sterile medium. The general operating flow direction is indicated by arrows. Additional connections or lines 111, 112 or 121, 122 can be provided on the first filter 110 and the second filter 120, particularly for sample collection and / or as connections for waste bags.
[0005] Each of the two filters 110, 120 can be individually inspected for integrity. In the case of the first filter 110, for example, a test connection 151 upstream of filter 110 is suitable. In the case of the second filter 120, for example, a test connection 131 upstream of filter 120 is suitable. For this purpose, test connections 131, 151 can be connected to the respective test apparatus via their respective test fluid filters (e.g., air filters) 132, 152. Test fluids can be sent to the first filter 110 and the second filter 120 respectively via lines 151 or 131, and can be discharged via lines downstream of their respective filters 110, 120 (e.g., 132). In this way, the integrity of each of the two filters can be individually tested, for example, by diffusion testing and / or bubble point testing. However, these integrity tests are very expensive, especially if the sterility of the entire system must be maintained simultaneously. Most importantly, the large number of components required for the test and their connections to test fluids flowing in different directions make the test critical to potential contamination.
[0006] Therefore, the object of the present invention is to inspect the integrity of a dual-filter assembly as simply and reliably as possible while ensuring sterility. This object is achieved as pointed out in the independent claims. Preferred embodiments are the subject of the dependent claims, or otherwise set forth in the following description.
[0007] Therefore, in one aspect, the present invention relates to a method for conducting integrity testing of a dual-filter capsule. The method includes providing a dual-filter capsule having a housing in which a first filter for a first filtering medium and a second filter for a second filtering medium are arranged. The two (i.e., at least two) filters are arranged one after the other in the flow direction of the medium to be filtered, such that during filtration, the medium to be filtered flows in its flow direction from the front chamber in the housing through the first filter to the gap between the first and second filters, and further through the second filter to or potentially to an outlet disposed in the housing, via which the filtered medium exits or can exit the dual-filter capsule. The housing has a (particularly closable) front chamber passage for supplying test fluid into the front chamber and a (particularly closable) gap passage for supplying test fluid into the gap.
[0008] Specifically, membrane filters are used as the first and / or second filters. This means that the first or second filter preferably comprises a first or second filter membrane. Particularly preferably, the first and / or second filter is designed in the form of a substantially cylindrical filter candle. In a preferred embodiment, during filtration, the medium to be filtered flows through the first and / or second filter membrane in a substantially radially inward direction. The first and / or second filter membrane is particularly preferably folded into a pleated structure. In particular, in a cylindrical arrangement with pleats, the large filter surface combined with relatively high flow uniformity increases the effective utilization of the filter membrane. Alternatively, the first and / or second filter can be designed as a planar filter.
[0009] Furthermore, the method includes providing a connecting line between the anterior chamber passage and the void passage for a (closable) fluid connection between the anterior chamber and the void. Here, at least the fluid connection to the void can be closed. For this purpose, the void passage itself or the connecting line can be closed accordingly, i.e., a corresponding valve may be included. When the fluid connection between the anterior chamber and the void is established via the connecting line, the connecting line specifically acts as a bypass to the actual flow through the first filter. However, preferably, the connecting line is used only for integrity testing, particularly in the second test phase described later, as a bypass and fluidly connected to the void. Otherwise, particularly during filtration, the connecting line remains substantially present (and connected), but the fluid connection to the void is interrupted.
[0010] The method now includes determining the integrity status of the dual-filter capsule, particularly the first and second filters, based on at least two test phases: a first test phase and a second test phase, and, if applicable, determining the possible seal between the housing and / or the filter and the housing. However, it should be noted that these two test phases (and the associated integrity checks) do not necessarily have to be performed in the order they are named herein. In particular, the second test phase may also occur before the first test phase. A compressible fluid, i.e., a gas, is preferably used as the test fluid.
[0011] For example, the first testing phase thus includes supplying test fluid into the anterior chamber, particularly via the anterior chamber passage, when the fluid connection from the connection line to the void is closed (or interrupted) (and preferably when the outlet is open). In this state, a first integrity check is performed. The first integrity check may specifically include bubble point testing and / or diffusion testing and / or pressure holding testing. Examples of possible integrity checks will be described in more detail later. In any case, in this first testing phase, it is desirable to introduce test fluid into the anterior chamber only via the anterior chamber passage, without allowing test fluid to enter the void directly from the outside and to the outside. In the first testing phase, the void may be fluidly connected to the environment (outside the housing) or the outlet of the dual-filter capsule, particularly via the void passage (e.g., through a three-way valve), for example for pressure equalization (e.g., through a sterile filter), but not connected to the connection line for the test fluid. Instead, in this first testing phase, only the test fluid is agitated through the first filter, and its behavior is examined. Here, the test fluid that has passed through the first filter can now at least partially accumulate in the gap and / or continue to reach the outlet of the dual-filter capsule via the second filter, wherein the outlet can also be closed or kept open depending on the operating mode of the first test phase to allow the test fluid to leave the housing.
[0012] Therefore, the first test phase can preferably be operated in two different test modes, which will be referred to below as the "static mode" and the "dynamic mode". Here, in the static mode, a state is set in which the same amount of test fluid is continuously supplied via the pre-chamber passage as passes through the first and second filters to exit via the outlet. Thus, a balance is established between the flow entering the void through the first filter and the flow exiting the void through the second filter. It can be assumed that, in this state, there is a constant test fluid pressure in the pre-chamber, in the void, and at the outlet. The pressure difference between the pre-chamber and the void on the one hand, and between the void and the outlet on the other hand (ideally also remaining constant over time in this mode) causes the test fluid to flow through the first and second filters respectively. Using the given target characteristics of the dual-filter capsule (or the first and second filters) of the integrity check type being performed, particularly in this test mode, the characteristic behavior can be expected with respect to the pressure in the pre-chamber on the one hand (or the pressure difference between the pre-chamber and the outlet) and the inflow of test fluid into the pre-chamber required to maintain the pressure in the pre-chamber (or the pressure difference between the pre-chamber and the outlet). If the actual characteristics deviate from the expected behavior, it can be assumed that at least one of the two filter stages (i.e., specifically one of the two filters themselves, their seal to the housing, or even the housing itself) is not intact. However, under this test mode, it is usually not possible to immediately determine which of the two filter stages may be faulty. However, combining the second test stage allows for conclusions to be drawn.
[0013] However, firstly, the dynamic mode used in the first testing phase of the preferred embodiment should be described. In particular, in this mode, it is especially advantageous to use a test gas as the test fluid, or at least during the test or before the start of the test, the void should not be completely filled with an incompressible test fluid. The dynamic mode is based on the assumption or operating condition that, after the test fluid is supplied to the pre-chamber or after the pressure of the test fluid in the pre-chamber is established, the evaluation as part of the first integrity check occurs within such a short time (check time) that this time (test time) is substantially shorter than the ratio of the (compressible) volume in the void to the target value of the test fluid flow rate through the first filter. "Substantially" should be specifically understood here to mean that the check time is no longer than about 20% of the quotient of the (compressible) volume in the void to the target value of the test fluid flow rate through the first filter, preferably no longer than about 10%, even more preferably no longer than about 5%, and most preferably no longer than about 2%. As the flow rate depends on the pressure in the anterior chamber or the pressure difference between the anterior chamber and the gap, preferably, the inspection time is also obeyed as a function of the selected inspection pressure or the selected pressure difference.
[0014] As a result, the pressure in the void did not change substantially during the inspection period, which was largely independent of the state of the second filter. Therefore, in this mode, the integrity state of the first filter stage (i.e., particularly the first filter or its seal towards the housing) can be determined specifically by the pressure in the pre-chamber (or the pressure difference between the pre-chamber and the void) and / or by the flow of test fluid into the pre-chamber. Thus, the dynamic mode is based on an inspection of the system's non-equilibrium state. However, it preferably begins from a known equilibrium state. In other words, preferably, the pressure and flow rate in the dual filter capsules are initially set to equilibrium before the pressure buildup in the pre-chamber for the first integrity test begins. Specifically, a state with equal pressure in the pre-chamber, the void, and the outlet can be considered such an equilibrium state that there is essentially no flow through the filter in that state.
[0015] The second testing phase involves simultaneously supplying test fluid into the anterior chamber (particularly via the anterior chamber passage) and into the void via the void passage (especially when the outlet is open). The anterior chamber is fluidly connected to the void via a connecting line, allowing pressure equalization to occur between the anterior chamber and the void. In this state, a second integrity check is performed. The second integrity check may specifically include bubble point testing and / or diffusion testing and / or pressure holding testing. The second integrity check preferably includes one or more of the same tests as the first integrity check.
[0016] The connecting line between the anterior chamber and the gap (as a bypass) used in the second testing phase can also be present / remain present during the first testing phase, in which case only the fluid connection to the gap is interrupted. In other words, the entire structure regarding the connecting line can remain intact during the integrity check, and even during subsequent (or even earlier) filtration. In particular, it is not necessary to separate individual lines and reconnect them in a different manner during the integrity test or between the integrity test and the filtration process. Therefore, the sterility of the entire system can be maintained in a particularly reliable manner.
[0017] Therefore, the method according to the invention makes it possible to examine the integrity of each of at least two filters assembled in a housing in two substantially independent measurements, allowing for a reliable statement on the integrity of each of the two filters individually and on the entire filter assembly, while requiring minimal intervention in the contellations provided and necessary for the purification filtration process to perform the integrity test. In particular, the integrity test according to the invention utilizes additional connections and lines that must be specifically provided for the integrity test and keeps the necessary switching processes, i.e., changes to connections during the test, to a minimum. This effectively prevents contaminants from being introduced into or transferred within the filter system, for example, due to (potentially unintentional) changes in flow direction within the test lines. Most importantly, the integrity test can be performed using only one source of test fluid (particularly the integrity test apparatus) without the need to disconnect and reconnect (in a changed manner) between test phases, and without the need for numerous valves that must be provided during or immediately before the test and / or braked afterward. In particular, no complex conversion is required between the integrity test and the actual filtration process. Therefore, the method according to the invention can be used very efficiently immediately before and immediately after the filtration process. Therefore, the dual-filter capsule, together with the test method according to the invention, can be used very easily and safely for integrity testing before actual filtration and / or after sterilization (on the factory side), i.e., in the pre-use-post-sterilization state, and especially immediately after filtration, to verify whether the filtrate was not sterilized due to a defective filter.
[0018] The method of the present invention is particularly suitable for use with dual-filter capsules in which two filters are integrally formed. Here, both filters of the dual-filter capsule are mounted within a common housing and, in particular, are securely connected and / or welded together. Optionally, the components of the dual-filter capsule, such as individual filters, can be secured together with screws and / or clamps, allowing the two elements to be connected to each other by screws and / or clamps. However, the integral design, in particular, prevents the filter system from being contaminated by impurities during assembly. Once the integrity of the dual-filter capsule has been checked, it can be used for filtration with high reliability.
[0019] For at least most tests preferred in this context, particularly when using a test gas as the test fluid, it is preferred to wet the first and / or second filters directly or indirectly with a wetting medium before determining the integrity status of the dual-filter capsules. In particular, a liquid (e.g., a solvent) also contained in the medium to be filtered can be used as a wetting medium. Water or aqueous solutions are particularly preferred for hydrophilic filter materials (e.g., membranes), and alcohols or alcohol / water mixtures are particularly preferred for hydrophobic filter materials (e.g., membranes).
[0020] As already mentioned, different types of integrity checks can be performed in a single testing phase. Therefore, the first and / or second integrity checks may specifically include bubble point testing and / or diffusion testing and / or pressure holding testing.
[0021] Bubble point testing, which may be performed specifically as part of the first and / or second integrity checks, will be described in more detail below. In particular, it represents a preferred non-destructive method for integrity checks performed within the scope of the invention. In this test, the filter to be tested is first wetted with a wetting liquid. The bubble point test is specifically performed using a test gas as the test fluid, wherein a pressure drop is established on the first and / or second filter by supplying the test gas into the pre-chamber. Specifically, in the case of the first test phase in dynamic mode, a pressure drop is substantially established on the first filter; in the case of the first test phase in static mode, a pressure drop is substantially established on both the first and second filters; and in the case of the second test phase, a pressure drop is substantially established on the second filter.
[0022] If the pressure drop at each filter is low enough, the wetting medium is retained within the pores of the respective filter, primarily through surface tension and capillary forces, thus creating a barrier for the test gas, which is essentially unable or at least not significantly able to penetrate the respective filter. The minimum pressure drop across the filter required to force the liquid wetting medium through the filter pores is a measure of the pore size according to the following formula:
[0023] (Equation 1)
[0024] ΔP corresponds to the bubble pressure (bubble point), i.e., the pressure drop across the filter, where a wetting medium with surface tension (e.g., water at approximately 72.75 mN / m; 2-propanol at approximately 21.7 mN / m) is forced through the filter by a test gas through a pore size... D The pores were examined, and gas penetration through the filter was tested, particularly using visible bubbles. θ Specify the wetting angle of the combination of wetting medium and membrane material used (e.g., CTA: 50° – 55°; PAN: 52° – 58°; PESU: 65° – 70°, each for water as the wetting medium).
[0025] Preferably, the first and / or second integrity checks are performed based on bubble point testing to determine the bubble pressure of the filter under test and compare it with a corresponding target value for the bubble pressure (particularly specified by the manufacturer). For this purpose, the pressure drop at the first or second filter is preferably set to, for example, about 80% of the specified desired value, and then continuously increased under observation until bubbles begin to form. If the measured bubble pressure is lower than the target value (particularly exceeding the permissible tolerance), it can be concluded that the corresponding filter, particularly the filter membrane, is defective.
[0026] Since almost no test gas penetrates the first filter below the bubble pressure, the first test phase within the framework of the bubble point test is preferably performed in the dynamic mode already described above. On the one hand, there is no need to wait for a static state to form. Instead, the possible increase in pressure in the void occurs so slowly that sufficient time is available to observe the initial formation of bubbles on the first filter after the pressure increase in the pre-chamber and before a significant increase in pressure in the void. On the other hand, independent inspection of both filters is directly possible, meaning that statements regarding the integrity of the first filter can be made solely as a result of the first test phase.
[0027] In another preferred embodiment, the first and / or second integrity checks include a diffusion test. This test also represents a preferred non-destructive method for integrity checks performed within the scope of the invention. The test is based on the principle that, under pressure differential (pressure drop across the filter), particularly below bubble pressure, gas molecules of the test gas (e.g., air, nitrogen, argon, rare gases, and / or other inert gases) diffuse through a filter wetted with a wetting medium, according to Fick's Law. The rate of gas diffusion (flow) through the filter depends, in particular, approximately proportionally to the pressure differential and (effective) filter area. In other words, the diffusion test measures the transmembrane diffusion flow through a wetted filter material, such as a membrane (first Fick's Law). Gas diffusion can be measured in various ways, such as by directly measuring the gas volume on the clean side (filter side) or the amount of gas to be replenished on the inflow side (residue side) to maintain the test pressure, or by determining the pressure drop after increasing the pressure on the clean side or shutting off a source of compressed gas or pressurized fluid on the inflow side (pressure holding test). In other words, the pressure holding test is a specific form of diffusion testing. In pressure holding tests, very precise pressure gauges are typically used to specifically record pressure changes on the inflow side caused by gas diffusion through the filter. Since it is essentially unnecessary to determine the airflow on the clean side of the filter, the risk of contamination of the sterile side of the filter is avoided.
[0028] Preferably, the first and / or second integrity checks are performed based on diffusion tests, thereby specifying target values (particularly specified by the manufacturer) for the bubble pressure of the filter under test. The pressure drop across the first or second filter is then preferably set to a value in the range of approximately 60% to approximately 90% of the predetermined desired value for, for example, the bladder pressure. Specifically, after a stabilization time for the diffusion rate, the gas flow rate or diffusion rate is measured, for example, within a measurement period of approximately 5 s to approximately 120 s, preferably approximately 10 s to approximately 1 minute, for example, within the range of approximately 20 s. This can be achieved, for example, by using a flow meter. If the measured gas flow rate or measured diffusion rate is outside (particularly greater than) the specified (particularly specified by the manufacturer) specifications, defects in the corresponding filter, particularly the filter membrane, can be inferred.
[0029] In a preferred embodiment, in addition to the pre-chamber passage for supplying test fluid into the pre-chamber, the void passage for supplying test fluid into the void, and the outlet, the housing also includes an inlet for supplying the medium to be filtered into the pre-chamber for the filtration process. In other words, in this case, the housing specifically has two separate inlets or connections to the pre-chamber for supplying the medium to be filtered on one hand and the test fluid on the other.
[0030] Alternatively, a single passage to the pre-chamber may be provided within the housing of the dual-filter capsule, through which the test fluid and the medium to be filtered are supplied to the pre-chamber—however, typically selectively rather than simultaneously. For this purpose, the corresponding lines for the medium to be filtered and the test fluid can be combined externally, and the individual supply lines can be shut off individually from each other.
[0031] The closure of the closable pre-chamber and / or the closure of the (preferably closable) inlet for supplying the filter media into the pre-chamber can also be explicitly formed by a clamping element and / or a clamping valve. Such a clamping element, such as a hose or a portion of a hose, can be at least partially deformable, particularly by clamping, thereby reducing or even preventing the passage or flow of media through the clamping element. This can be achieved, for example, in a progressively adjustable manner. Alternatively, clamping can be performed such that flow is substantially completely blocked or substantially completely permitted. Externally controllable clamping elements make it possible to control the inflow and / or flow through line elements such as hoses without disturbing the internal space and potentially contaminating the media therein.
[0032] Preferably, the membrane of the first filter has a larger pore size than the membrane of the second filter. The first filter with a slightly larger pore size is designed to filter out larger suspended matter, such as lipid aggregates or other particles, from the medium, and thus release the second filter, which is specifically designed to filter out cells. In this way, premature clogging of one of the filters or excessive accumulation of suspended matter in the pores can be prevented.
[0033] Preferably, the pore size of the first filter has a value in the range of about 0.3 μm to about 0.6 μm. Optionally or additionally, the pore size of the second filter preferably has a value in the range of about 0.1 μm to about 0.3 μm, particularly about 0.1 μm to about 0.2 μm. Preferably, at least the second filter is a sterile filter designed as a filter medium, such that, as much as possible, all suspended matter larger than about 0.1 μm to about 0.2 μm is filtered out, especially cells, bacteria, yeast, fungal spores, endospores, and / or viruses. In particular, the first filter is designed as a pre-filter to prevent coarse particles or suspended matter from reaching the second filter, which is preferably a sterile filter, and to prevent it from "clogging" or becoming blocked. The dual-filter capsule system is preferably designed such that the sterile filter can only filter out bacteria or protozoa and / or viruses from the medium.
[0034] Optionally, the pore size of the first filter roughly corresponds to that of the second filter. If the pore sizes of the two filters are approximately the same, the second filter can be used as a redundant filter in the event that the first filter fails during operation. Redundant aseptic filtration means that from a validation perspective, a single filter is sufficient for aseptic filtration. For example, for safety reasons, an additional second aseptic filter, particularly a 0.2 µm filter (referred to as a "secondary filter," but sometimes also called a "police filter" or "redundant filter"), is used, and the filter closest to the filling point is the first filter (primary filter). In particular, when the pore sizes of the first and second filters are the same or at least similar, the pore sizes of the membranes of the first and second filters preferably have values in the range of about 0.05 μm to about 0.4 μm, particularly about 0.1 µm to about 0.2 µm.
[0035] If the primary filter fails the integrity test after use, the secondary filter will be tested. If it passes the integrity test, the filter media does not need to be discarded, as the filtration process essentially occurs through the secondary filter. In this case, both filters should be tested before and after sterilization according to EU-GMP requirements for PUPSIT (Pre-use-Post-sterilization Integrity Test). Otherwise, the secondary filter may not be considered a valid sterilized filter after use. After filtration using this dual-filter capsule, it is sufficient to test the primary filter first. The secondary filter should only be tested after use if the primary filter fails the integrity test.
[0036] Preferably, at least one filter is designed as a substantially cylindrical filter candle. This cylindrical filter candle, with a height particularly larger than the diameter of a cylindrical candle, has the advantage of creating a particularly large surface area for the pleated structure, thereby allowing for the filtration of the maximum possible amount of media. The pleated filter membrane is arranged substantially in a cylindrical shape within the filter candle. The height of the cylindrical filter candle may be referred to as the cylindrical height.
[0037] Therefore, a filter candle is a preferred filter. For example, a core (perforated inner tube) and an outer tube (backflow preventer) concentrically surrounding the core are provided, such that an annular gap is formed between the core and the outer tube (shell). Preferably, the pleated filter membrane is arranged in a pleated manner, with the pleats extending from their respective pleated edges abutting the outer tube in the direction of the inner tube to their respective pleated tips, or arranged along the circumference of the annular gap. In particular, the core represents part of the filter candle's housing and serves as a support.
[0038] Alternatively, the filter may have only substantially flat filter elements, such as a flat filter or a perforated sheet arranged between two spaces above the opening. However, in this case, the filtration area is relatively small.
[0039] According to another aspect, the present invention relates to a system for performing integrity testing, comprising:
[0040] A dual-filter capsule has a housing in which a first filter and a second filter are arranged one after another in the flow direction of the medium to be filtered, such that during filtration, the medium to be filtered flows from the front chamber in the housing through the first filter to the gap between the first and second filters in its flow direction, and flows forward through the second filter to the outlet. The housing has a front chamber channel for supplying test fluid into the front chamber and a gap channel for supplying test fluid into the gap.
[0041] A connecting line between the anterior chamber passage and the void passage for fluid connection between the anterior chamber and the void, wherein at least the fluid connection to the void may be closable; and
[0042] The integrity inspection device is designed to perform the following two test phases and determine the integrity status of the dual-filter capsules based on these phases:
[0043] -- The first testing phase includes: supplying test fluid to the anterior chamber with the fluid connection between the connector and the gap closed, and performing a first integrity check; and
[0044] -- The second testing phase includes: simultaneously supplying test fluid into the pre-chamber and into the void via a void channel, the pre-chamber being fluidly connected to the void via a connecting line, thereby achieving pressure equalization between the pre-chamber and the void, and performing a second integrity check.
[0045] The integrity checking device is specifically designed to perform at least a first test phase and / or a second test phase in a manner that is at least partially automated. Specifically, valves can be automatically controlled, i.e., opened and / or closed automatically or by computer control, and pressure can be automatically applied and regulated. Additionally, the diffusion rate can preferably be automatically determined and / or a bubble point test can be performed, and the associated bubble point can be determined. For example, the pressure can also be slowly increased at the inlet, thereby determining the time point until the applied compressed air passes through one or two filters and reaches a predetermined diffusion value. Such pressure can then correspond to the bubble point. Preferably, the interior of the dual-filter capsule can be at least partially inflated and / or deflated by means of the integrity checking device, particularly via passages to the anterior chamber and / or voids.
[0046] The system preferably includes at least one test fluid filter, which is preferably designed as a sterile filter to filter the test fluid before it enters the anterior chamber or void via the anterior chamber passage or void passage. Depending on the application, sterilization of the pressurized fluid, such as compressed air, before introducing it into the dual-filter capsule is necessary or desirable. The sterile filter used to filter the pressurized fluid prevents contaminants from entering the interior of the dual-filter capsule along with the pressurized fluid, particularly between the two filters. This ensures that sterile conditions are maintained within the dual-filter capsule even during integrity checks.
[0047] According to another aspect, a computer program product includes instructions that, when executed by a computing unit, particularly an integrity checking device, cause the latter to at least partially perform the method or the steps of the method.
[0048] The following description of embodiments and examples will be based on the accompanying drawings. The features described herein may be considered optional and / or combined with other features, unless they are mutually exclusive.
[0049] Figure 1 This is a schematic cross-sectional view of an exemplary integrity check setup for a dual-filter capsule;
[0050] Figure 2 This is a schematic cross-sectional view of an exemplary integrity check setup for a dual-filter capsule equipped with more than two filters;
[0051] Figure 3A yes Figure 1 A schematic diagram of the setup to illustrate an exemplary first test phase of the dynamic mode;
[0052] Figure 3B yes Figure 1 A schematic diagram of the setup to illustrate an exemplary first test phase in static mode;
[0053] Figure 4 yes Figure 1 A schematic diagram of the setup to illustrate an exemplary second testing phase;
[0054] Figure 5A -E schematically illustrates the various states in the filtering process (including the preparation and implementation of integrity tests) to show what integrity tests may include;
[0055] Figure 6A -F schematically illustrates the various states in the filtering process (including the preparation and implementation of integrity tests) to further illustrate what integrity tests may include;
[0056] Figure 7An exemplary arrangement for integrity checks of a conventional dual-filter system is shown.
[0057] Figure 1 An exemplary schematic cross-sectional view of a dual-filter capsule 10 is shown. The dual-filter capsule 10 includes a preferably substantially cylindrical housing 12, wherein, in this variant, an inlet 14 and an outlet 16 are provided for supplying the filter medium M, and the filter medium M'' (i.e., the medium M after filtration) can be discharged via the outlet 16. Within the housing 12, a first filter 18 and a second filter 20 are arranged one after the other from the inlet 14 to the outlet 16 in the direction of medium flow.
[0058] Within housing 12, a first filter 18 fluidly separates the pre-chamber 22 from the void 24. The void 24 is then fluidly separated from the outlet 16 by a second filter 20 (in the sense that, at least in conventional filter operation with a complete filter capsule, any fluid flow between the void 24 and the outlet 16 must pass through / through the filter 20 and thus be filtered). During filtration, the medium M to be filtered thus enters the pre-chamber via inlet 14. In the first of two consecutive filtration steps in the flow direction, the medium M to be filtered enters the void 24 from the pre-chamber 22 through the first filter 18 and is thus at least pre-filtered or partially filtered. Then, the at least partially filtered medium M' passes from the void 24 through the second filter 20 to the outlet 16, where it exits housing 12 as filtered medium M''.
[0059] In the variant shown, the first filter 18 and the second filter 20 are each designed as filter candles. Since these filter candles are constructed substantially similarly, the following description does not distinguish between the first and second filters, even though they may differ and are intended to differ, for example, regarding their pore size, depending on the specific application.
[0060] The filter candle preferably includes a core 26, particularly as a cylindrical support structure having multiple pores, preferably arranged in a mesh-like manner, and / or formed as a lattice structure. For example, the core 26 can be formed as a perforated cylindrical tube and / or a cylindrical mesh. In particular, the core 26 can therefore be through which fluids, particularly medium M and the test fluid described later, flow with essentially no significant flow resistance.
[0061] Preferably, a filter structure 28 folded into a pleated shape is arranged around the support structure (core 26). The filter structure 28 preferably includes at least one filter membrane, and particularly preferably at least one nonwoven layer on which or therein the filter membrane is disposed. In a preferred embodiment, the filter membrane is embedded between two nonwoven layers. More preferably, a series of layers having multiple filter membranes, each embedded between nonwoven layers, may also be provided.
[0062] Preferably, the filter candle also includes an outer tube 30 surrounding the filter structure 28 and the core 26, and specifically serves as a backflow preventer 30 to prevent potential damage to the filter structure 28 in the event of back pressure buildup in the filter candle (i.e., against the actual flow direction). The core 26 and / or the backflow preventer 30 are particularly formed of a plastic suitable for sterilization. For example, polypropylene and / or polytetrafluoroethylene and / or another polymer are suitable as construction materials, at least for components of the dual filter capsule, such as the core 26 and / or the backflow preventer 30. Optionally or additionally, the core 26 and / or the backflow preventer 30 and / or the housing may also comprise metal.
[0063] In dual-filter capsules having filter candles of the type described as a first filter 18 and / or a second filter 20, which are preferably used within the scope of this invention, the conventional flow direction during filtration through the filter candles preferably extends substantially radially inward, such as... Figure 1 As shown. Therefore, the anterior chamber 22 preferably also extends in the region radially outer of the first filter candle (first external space 32). The gap 24 then extends in the region radially inner of the first filter candle (first internal space 34) and the region radially outer of the second filter candle (second external space 36). Then, the region radially inner of the second filter candle (second internal space 38) is directly connected to the outlet 16. In order to seal the first internal space 34 with the anterior chamber 22 or to seal the second internal space 38 with the gap 24, each of the two filter candles has a bottom cover 40 as an end wall. In order to seal the first external space 32 with the gap 24, an intermediate wall 42 is provided to connect the first filter candle to the outer wall of the housing 12. In principle, using Figure 1 The structure shown allows for the modular construction of the entire filter capsule, making it possible not only to arrange two, but also three or more filters one after another in the manner shown.
[0064] For example Figure 1 As shown, the dual-filter capsule 10 includes an anterior chamber channel 44 and a void channel 46, through which the anterior chamber 22 and the void 24 can be fluidly connected or connected via a connecting line 48. The anterior chamber channel 44 and the void channel 46 are used to supply test fluids, particularly test gases, to the anterior chamber 22 or the void 24. Preferably, the fluid connection of the connecting line 48 to the anterior chamber 22 and the void 24 can be selectively closed – specifically, without disconnecting the mechanical connection of the connecting line 48 from the anterior chamber channel 44 to the anterior chamber 22 or from the void channel 46 to the void 24, i.e., without opening the previously closed fluid passage along the connecting line and the passage to the interior of the housing 12. Therefore, fluid flow can be selectively interrupted or controlled without compromising the sterility of the system.
[0065] This can be achieved, in particular, by their respective valves (pre-chamber channel valve or intermediate chamber valve). Such valves can be clampable tubular elements, clamping elements, or clamp valves. Specifically, the connecting line 48 itself can be designed as a clampable or compressible hose connection, or at least include a clampable / compressible hose portion to the pre-chamber channel 44 or the void channel 46. The fluid connection of the connecting line 48 to the pre-chamber 22 and the void 24 is preferably closed during filtration. This is achieved through… Figure 1 The "X" in the text represents...
[0066] To supply the test fluid for integrity checking to the dual-filter capsule 10, the connecting line 48 preferably has a connection to the test device line 50, in which a test fluid filter 52 (particularly as a sterile filter) is disposed, and which leads to the integrity checking device (not explicitly shown). The test fluid can optionally be supplied to the anterior chamber 22 and / or the void 24 via this fluid connection. In particular, the test fluid pressure and / or test fluid flow rate can also preferably be measured and / or adjusted in this manner. For example, the Sartocheck® 5 device from Sartorius can be used as an integrity checking device.
[0067] Before determining the integrity status of the dual-filter capsule 10, it is preferable to ensure that both filters are wetted. This is guaranteed by the fact that the filtration process has already occurred before the integrity status is determined. Alternatively, it is preferable to introduce a wetting liquid similar to the filtration process, particularly using... Figure 1 The method shown is also introduced via inlet 14 to wet the filter structure.
[0068] Figure 2 An exemplary schematic cross-sectional view of another dual-filter capsule 10 is shown, which in this embodiment even includes more than two filters. Three filters are clearly shown. Figure 2 However, in principle, more filters can also be accommodated in the same, preferably substantially cylindrical, housing 12. Regarding... Figure 1 The explanation of the dual-filter capsule 10 can also be applied to Figure 2 The dual-filter capsule 10 eliminates the need for repeated, precise descriptions of similar components (especially if they are provided with the same reference numerals). Therefore, within the housing 12, a first filter 18, an intermediate filter 19, and a second filter 20 are arranged one after another in the direction of media flow from inlet 14 to outlet 16. Here, the invention can be selectively applied to at least two of three or more filters, particularly selectively applied to at least two filters that are directly continuous in the direction of media flow. However, preferably, the integrity of all (e.g., three or more) filters is checked by means of the method according to the invention, which will be described in more detail later.
[0069] Inside housing 12, a first filter 18 fluidly separates the pre-chamber 22 from the (first) void 23. The (first) void 23 is then separated from the (second) void 24 by an intermediate filter 19, which in turn is separated from the outlet 16 by a second filter 20 (fluidly) (in the sense that any fluid flow between inlet 14 and outlet 16 must pass through / through the respective filters 18, 19, 20, and thus be filtered during conventional filter operation with a fully complete filter capsule). During filtration, the medium M to be filtered thus enters the pre-chamber 22 directly or indirectly via inlet 14. In the first of at least three consecutive filtration steps in the flow direction, the medium M to be filtered enters the (first) void 23 from the pre-chamber 22 through the first filter 18, and is thus at least pre-filtered or partially filtered. Then, the at least partially filtered medium M' enters the (second) void 24 from the (first) void 23 through the intermediate filter 19, and is thus further filtered. Finally, the further filtered medium M' passes through the second filter 20 from the (second) gap 24 to the outlet 16, where it exits the housing 12 as the filtered medium M''.
[0070] In the variant shown, at least three filters are each designed as filter candles, as if combined. Figure 1 As described. Similar to Figure 1 Implementation plan, Figure 2 The implementation also includes an anterior chamber passage 44 and a (second) gap passage 46, and in this case, at least one (first) gap passage 45 is additionally included, through which the anterior chamber 22, (second) gap 24, or (first) gap can be fluidly connected or via a connecting line 48. The anterior chamber passage 44 and gap passages 45, 46 are used to supply test fluids, particularly test gases, to the anterior chamber 22 or gaps 23, 24. The fluid connection of the connecting line 48 is preferably to the anterior chamber 22 and gaps 23, 24—without requiring the mechanical connection of the connecting line 48 via the anterior chamber passage 44 to the anterior chamber 22 or via the gap passages 45, 46 to the gaps 23 or 24, i.e., without requiring the fluid passage along the connecting line and the passage to the interior of the housing 12 to be opened simultaneously. Therefore, fluid flow can be selectively interrupted or controlled without compromising the sterility of the system. This can be achieved, in particular, by the respective valves, as already combined Figure 1 As described through examples.
[0071] Otherwise, preferably, with Figure 1 All explanations relating to the first and second filters can be applied directly or indirectly to the combination of the first filter 18 and the intermediate filter 19, which in turn relates to... Figure 1The second filter (with the intermediate space 23 therebetween) is equivalent to, or applied to, a combination of intermediate filters 19, which is then combined with... Figure 1 The first filter, the pre-chamber 23, and the second filter 20 are equivalent.
[0072] The following will be referenced Figure 3A , 3B Sections 4 and 5 describe exemplary determinations of the integrity status of the dual-filter capsule 10 based on at least two test phases. Figure 3A and 3B The first testing phase is specifically shown. Figure 3A The first integrity check in dynamic mode is shown, and Figure 3B The first integrity check in static mode is displayed. Finally, Figure 4 The second testing phase is shown.
[0073] Therefore, in Figure 3A In the preferred first test phase shown, at least the fluid connection between the connecting line 48 and the gap 24 is closed, except for the inlet 14. This is achieved through... Figure 3A The "X" in the region of the void passage 46 indicates this. Test gas is now supplied to the pre-chamber 22 via the pre-chamber passage 44 through the connecting line 48, which is fluidly connected to the pre-chamber 22. This establishes a pressure difference between the pre-chamber 22 and the void 24, causing the test gas to partially penetrate the first filter 18. The airflow is indicated by arrows. The first integrity check is performed in this way, for example, in the form of a bubble point test and / or a diffusion test and / or a pressure holding test. Depending on the test method, the pressure in the pre-chamber 22 is measured and / or the airflow of the test gas into the pre-chamber 22 is measured and / or regulated. The integrity of the first filter 18 can be inferred from the respective measured or controlled variables, particularly in a test-specific manner as described. In particular, in Figure 3A In the illustrated implementation, the test is performed in dynamic mode. The integrity check is performed so briefly or rapidly that the pressure in the gap 24 hardly changes due to the airflow through the first filter 18 during the test.
[0074] Figure 3BAn alternative variant is schematically illustrated, in which the first test phase is performed in a static mode. While in dynamic mode, whether output 16 is open or closed during the first integrity check is generally not decisive, output 16 should be open in static mode. Specifically, in static mode, the goal is to establish a continuous airflow from connection line 48 through pre-chamber passage 44 into pre-chamber 22, through first filter 18, into void 24, and through second filter 20 to outlet 16. In this fixed fluid series connection, the pressure drop across the two filters is a direct measurement of their fluid resistance, and measurements of total pressure and / or flow rate can be used to draw conclusions about the series connection of the two filters, particularly whether they meet specified specifications regarding bubble pressure, diffusion, and / or pressure holding values. However, depending on the test procedure, only one statement about the combination of the two filters is generally possible. Deviations from specifications do not necessarily allow for the conclusion that one of the two filters does not correspond to or corresponds less to the specifications. However, such a statement can at least be confirmed in conjunction with the second test phase.
[0075] at last, Figure 4 An exemplary implementation of the second testing phase is shown. In this testing phase, the anterior chamber 22 and the gap 24 are connected via a connecting line 48, such that the supplied test gas flows into the anterior chamber 22 and the gap 24 at substantially the same pressure. Therefore, the connecting line 48 induces pressure equalization between the anterior chamber 22 and the gap 24. Regardless of the type of integrity test performed, and particularly regardless of the test pressure applied via the second filter 20, it is ensured on the one hand that the first filter 18 is not damaged by reverse pressure. On the other hand, it is ensured that the test gas introduced into the gap 24 does not diffuse out through the first filter 18 (as a rearward flow), but can only flow through the second filter 20 to reach the outlet 16. The corresponding airflow of the test gas in this second testing phase... Figure 4 This is indicated by an arrow. This ensures that any pressure and / or airflow values measured or controlled for the second integrity check represent only the characteristics of the second filter 20. Even if the first filter 18 deviates significantly from the required specifications, the evaluation of the second filter 20 will not be falsified in the second testing phase.
[0076] refer to Figure 3A , 3B The test phases described in section 4 can also be applied to, for example... Figure 2 The dual-filter capsule shown has two test stages that can be used, for example, to test a combination of the first filter 18 and the intermediate filter 19 (as the second filter) and / or a combination of the intermediate filter 19 (as the first filter) and the second filter 20. Another option, using additional test stages to test all three filters, will be described later.
[0077] Figures 5A-5EAn exemplary sequence of method steps is shown to illustrate how integrity testing can be embedded in a filtration process. Arrows indicate the flow direction of the respective fluids, and the mark "X" indicates a corresponding closed valve or line.
[0078] For example, Figure 5A The wetting process of the filter structure in the dual filter capsule using wetting medium BM is illustrated. In this wetting process, the fluid connection is preferably closed via the pre-chamber passage and the void passage. Furthermore, the inflow of the filter medium is temporarily shut off. The wetting medium BM flows through both filters and, after leaving the dual filter capsule, is preferably discharged via an outlet through a separate drain pipe. Therefore, the wetting medium can be processed individually.
[0079] Figure 5B The schematic illustration shows the status during the subsequent first testing phase, as shown in the example reference. Figure 3A (or Figure 3B As described above. Specifically, the inlet and void passages are closed, while the anteroom passage is open. Test gas is supplied to the anteroom via the anteroom passage for the first integrity check.
[0080] Figure 5C The schematic diagram illustrates the status of the second testing phase, as shown in the example reference. Figure 4 The description continues. Even though this second test phase is shown here after the first test phase, the two test phases can be performed in reverse order. Specifically, the inlet is closed, while, unlike in the first test phase, both the anterior chamber passage and the void passage are open. In this case, the outlet is also open. Here, the test gas is introduced into the anterior chamber and the void. Due to the matching pressure in the anterior chamber and the void, there is no net flow of test gas through the first filter. Any observed flow of test gas is due to flow through the second filter.
[0081] If both filters pass the integrity test, a dual-filter capsule can be used for filtration, such as... Figure 5D As schematically illustrated, the medium M to be filtered flows through two filters via the inlet, enters the dual filter capsule, and exits as filter medium M''. The medium to be filtered is preferably supplied via a separate channel. In this case, the channel previously opened for supplying the wetting medium is preferably closed. The separate drain pipe for the wetting medium is also closed. Therefore, the drain pipe for the filter medium is open. The anterior chamber channel and the void channel are also preferably closed.
[0082] After the filtration process is complete, it is preferable to force the residual liquid out of the pipeline, such as... Figure 5EAs shown. The piping system can be emptied downstream of the outlet by opening another channel after the outlet of the dual filter capsule and closing the outlet, for example, by introducing compressed air. Integrity testing may also be performed after the filtration process, as an alternative to or supplement to the integrity test prior to the filtration process.
[0083] Figures 6A-6F Another exemplary sequence of method steps is shown to illustrate how integrity testing can be embedded in the filtering process, where the dual-filter capsule is equipped with an additional filtering stage. In this implementation (e.g., according to...), Figure 2 Dual-filter capsules can even be used as triple-filter capsules. However, since at least two filter stages continue to operate one after the other, it is still understood here as an implementation of a dual-filter capsule.
[0084] For example, Figure 6A The wetting process of the filter structure in the dual filter capsule using wetting medium BM is illustrated. In this wetting process, the fluid connection via the pre-chamber passage 44 and the void passages 45, 46 is preferably closed. Furthermore, the inflow of the filter medium is preferably shut off. The wetting medium BM flows through all (at least three) filters and, after leaving the dual filter capsule, is discharged via an outlet, preferably through a separate drain pipe. Therefore, the wetting medium can be individually configured.
[0085] Figure 6B The schematic illustration shows the status during the subsequent first testing phase, as shown in the example reference. Figure 3A (or Figure 3B As described in the description. In this case, specifically, inlet 14 and the void passage are closed, while the antechamber passage 44 is open. Test gas is introduced into the antechamber via the antechamber passage 44 and a first integrity check is performed.
[0086] Figure 6C The diagram schematically illustrates the state during the second testing phase. Specifically, in this case, inlet 14 is closed, while, unlike in the first testing phase, both the anterior chamber passage 44 and the first void passage 45 are open. The outlet is also open in this case. Here, test gas is introduced into the anterior chamber and the first void. Due to the matching pressure in the anterior chamber and the first void, there is no net flow of test gas through the first filter. Any observed flow of test gas may contribute to the flow through the second filter.
[0087] Figure 6DThe state in the third test phase is schematically shown, similar to the test phase already described with reference to Figure 3. Specifically, inlet 14 is closed, while the anterior chamber passage 44 and the two void passages 45, 46 are open. In this case, the outlet is also open. Here, test gas is introduced into the anterior chamber and voids. Due to the matching pressure in the anterior chamber and voids, there is no net flow of test gas through the first and second filters. Any observed flow of test gas may contribute to the flow through the third filter. The three test phases do not necessarily have to be performed in the order described, but can be performed in different orders.
[0088] If all three filters pass the integrity test, filtration can be performed using a dual-filter capsule (in this case, even with three filters), such as... Figure 6E As illustrated schematically, the medium M to be filtered flows through all three filters into the dual filter capsule via the inlet and exits as filter medium M''. After the filtration process is complete, it is preferable to expel the residual liquid from the pipeline, such as... Figure 6F As shown.
[0089] Integrity checking devices can be specifically designed to control, monitor, or execute all or individual steps of a method in a manner that is at least partially automated. In particular, for example, valves, pumps, bypass and / or pipeline openings and closings, gas and / or liquid pressures, temperature elements, displays and / or warning lights or warning signals can be controlled by integrity checking devices.
[0090] The exemplary proof-of-principle measurements listed below demonstrate that the integrity test of the dual-filter capsule according to the invention yields the same results as the integrity test of two identical but separate filters. The proof-of-principle measurements are based on the method according to the invention to demonstrate its feasibility and reliability. In particular, these proof-of-principle measurements are based on diffusion tests and bubble point tests. The filters present in the dual-filter capsule are compared with filters identical to these filters but tested separately. In other words, these results come from filters not installed in the dual-filter capsule and identical to filter candles present in the dual-filter capsule and tested using the integrity test according to the invention. Combinations of different filter models used to demonstrate the feasibility and effectiveness of the integration test according to the invention are described by way of example. In the filter housings of the following examples, two filter candles are always installed in a “tandem” configuration.
[0091] Common filter models, referred to as "BH1" and "BH9," were tested. These names refer to the so-called overall height, i.e., the length of the essentially cylindrical filter candle. Test elements for constructing the filter candle can have a combination of filter sizes BH9 / BH9 or BH1 / BH1. The characteristic dimension of the filter model designated BH9 is approximately 0.18 m.2 The filter area. The characteristic dimension of the filter model named BH1 is a filter area of approximately 0.55 m². Furthermore, these names are always used to refer to the characteristic filter area.
[0092] The following models in a dual-filter capsule can be examples of structures that have already been tested:
[0093] First filter Second filter
[0094] Sartopore 2, 0.2 µm BH9 + Sartopore 2, 0.2 µm BH9
[0095] Sartopore 2, 0.2 µm BH1 + Sartopore 2, 0.2 µm BH1
[0096] The term "Sartopore" refers to an exemplary filter type, while the specification "0.2 µm" refers to the membrane's pore size. Both the diffusion rate and bubble pressure (bubble point) depend on various parameters, such as the temperature typically corresponding to room temperature during measurement, and the solvent used in the integrity test. Diffusion also depends on the overall height of the filter candle and, therefore, on the filter area.
[0097] A) First test setup:
[0098] The following limits are available: for Sartopore 2, with an pore size of 0.2 µm and a test pressure of 2.5 bar:
[0099]
[0100] The first example of a dual-filter capsule:
[0101] The integrity of two filters was tested, each with a diameter of approximately 0.18 m. 2 The filter area.
[0102] First filter: Sartopore 2, pore size 0.2 µm, BH9;
[0103] Second filter: Sartopore 2, pore size 0.2 µm, BH9.
[0104] Therefore, in this proof-of-principle test, two identical filters are installed in a housing, and their integrity test is compared with two integrity tests of each of the individual identical filters to demonstrate the feasibility and effectiveness of the integrity test according to the invention.
[0105]
[0106] During the measurement, the integrity of the individual filters is known. For the diffusion rate in the diffusion test, comparable values exist for the first and second filters as individual filters, as well as within the measurement accuracy range, in the dual-filter capsule. Although the first filter in the dual-filter capsule does not have a bubble point for the bubble point test, the values for the individual filter assembly and the second filter in the dual-filter capsule show comparable values. All measured diffusion values are below the aforementioned upper limit, and all measured bubble point values are above the aforementioned lower limit. Therefore, this proof-of-principle measurement demonstrates that, using the method according to the invention, the integrity of the two filters in the dual-filter capsule can be tested as reliably as in the individual assembly.
[0107] Second example of a dual-filter capsule:
[0108] The integrity of two filters, each with a diameter of approximately 0.55 m, was tested. 2 The filter area.
[0109] First filter: Sartopore 2, pore size 0.2 µm, BH1;
[0110] Second filter: Sartopore 2, pore size 0.2 µm, BH1.
[0111] Once again, in this proof-of-principle test, two identical filters were installed in a housing; however, they had different filter areas compared to the first instance.
[0112]
[0113] The second example also demonstrates that, based on comparable values of diffusion and bubble point, the method according to the invention can test two filters mounted in a dual-filter capsule within a housing with the same reliability as the testing method for a single filter. In this example, the bubble point of the first filter in the dual-filter capsule was also recorded. Fluctuations in the value can be attributed to differences in the wettability of the pleated structure.
[0114] Another implementation includes integrity testing of the assembly of a pre-filter (e.g., Sartopore 2, 0.45 µm pore size) integrated into the housing, followed by sterile filter (Sartopore 2, 0.2 µm pore size).
[0115] B) Second test setup:
[0116] First filter Second filter
[0117] Sartopore 2, 0.45 µm BH9 + Sartopore 2, 0.2 µm BH9 (Dual Filter Capsules)
[0118] Sartopore 2, 0.45 µm BH1 + Sartopore 2, 0.2 µm BH1 (Dual Filter Capsules)
[0119] The two dual-filter capsules are substantially different in their overall height. Therefore, integrity tests were performed on two dual-filter capsules with different filter areas but the same pore size combination. In this proof-of-concept test, for each dual-filter capsule, two different filters with different pore sizes were installed in a housing, and their integrity tests were compared with two integrity tests of each individual identical filter.
[0120] The following limits are available: For Sartopore 2, pore size 0.45 µm, test pressure 1.7 bar:
[0121]
[0122] The first example of a dual-filter capsule:
[0123] First filter: Sartopore 2, pore size 0.45 µm, BH9;
[0124] Second filter: Sartopore 2, pore size 0.2 µm, BH9.
[0125]
[0126] Second example of a dual-filter capsule:
[0127] First filter: Sartopore 2, pore size 0.45 µm, BH9;
[0128] Second filter: Sartopore 2, pore size 0.2 µm, BH9.
[0129]
[0130] In both instances, the two filters in each instance are substantially different in their pore size. In both proof-of-concept tests, two dissimilar filters with the same cylindrical length (overall height) were mounted in a housing, each with a different pore size. Integrity tests of the dual-filter capsule were compared with two integrity tests of each individual identical filter. In both instances, the integrity of both filters was tested, each with approximately 0.18 m...2 The filter area.
[0131] Based on the relatively similar results of diffusion tests for the dual-filter capsule and the single dual-filter (individual double), it can also be shown in these two examples that the integrity test of the dual-filter capsule according to the invention works as reliably as the integrity test of the single dual-filter. All values are within the allowable range, limited by the limits specified above.
[0132] The measurements from both the diffusion test and the bubble point test indicate that the integrity test of the dual-filter capsule according to the invention is comparable to that of the single dual filter in this example. All values are within the permissible range, limited by the aforementioned limits. As mentioned above, the deviation is due to differences in wettability, which is unavoidable.
[0133] A third example of a dual-filter capsule:
[0134] First filter: Sartopore 2, pore size 0.45 µm, BH1;
[0135] Second filter: Sartopore 2, pore size 0.2 µm, BH1.
[0136] The two filters are also substantially different in their pore size. In this proof-of-concept test, two non-identical filters with different pore sizes were installed in a housing, and their integrity test was compared with two integrity tests of their respective individual identical filters. The integrity of both filters was tested, each with approximately 0.55 μm. 2 The filter area.
[0137]
[0138] The third example also shows that the measurement data from the diffusion test and bubble point test of the second filter indicate that the integrity test of the dual-filter capsule according to the invention is comparable to the integrity test of a single dual filter.
[0139] The examples mentioned demonstrate the feasibility and effectiveness of the method according to the invention, as well as the comparability of the reliability of the integrity test with that of the individual integrity tests of a single dual filter.
[0140] C) Third Test Setup
[0141] The following considers the case where the filter is intentionally damaged, to demonstrate that the incompleteness of the filter in the dual filter capsule 10 can be detected as reliably as in a single filter assembly.
[0142] The first example of a dual-filter capsule:
[0143] First filter: Sartopore 2, pore size 0.2 µm, BH9;
[0144] Second filter: Sartopore 2, pore size 0.2 µm, BH9.
[0145] The second filter has serious defects.
[0146]
[0147] When the integrity of the single filter assembly and the first filter in the dual filter capsule is determined to be intact, the integrity measuring device automatically stops testing the second incomplete filter in the single filter assembly and the dual filter capsule. This example is intended to demonstrate that the integrity test according to the invention can also reliably determine the incompleteness of a defective filter in a dual filter capsule by means of diffusion testing and bubble point testing.
[0148] Therefore, the feasibility and effectiveness of the integrity test according to the present invention have been demonstrated in different instances.
[0149] Reference list of numbers
[0150] 10 Dual-Filter Capsules
[0151] 12. Shell
[0152] 14 Entrances
[0153] 16 Exports
[0154] 18 First Filter
[0155] 19. Intermediate filter or first / second filter
[0156] 20 Second Filter
[0157] 22 front room
[0158] 23. Anterior chamber or (first) gap
[0159] 24 (Second) Gap
[0160] 26 cores
[0161] 28. Filter Structure
[0162] 30 Backflow preventer
[0163] 32 External space of the first filter
[0164] 34 Internal space of the first filter
[0165] 36 External space of the second filter
[0166] 38. Internal space of the second filter
[0167] 40 end wall, bottom cover
[0168] 42 Intermediate wall
[0169] 44. Antechamber access
[0170] 45. Anterior chamber passage or (first) gap passage
[0171] 46 (Second) Gap Channel
[0172] 48 Connecting wires
[0173] 50 Test equipment pipeline
[0174] 52 Test fluid filter
[0175] M is the medium to be filtered.
[0176] M' is the medium used for partial filtration.
[0177] M'' Filtering medium
[0178] BM wetting medium
[0179] TG test gas
Claims
1. A method for conducting an integrity test on a dual-filter capsule (10), comprising: The dual-filter capsule (10) is provided, having a housing (12) wherein a first filter (18, 19) and a second filter (19, 20) are arranged one after another in the flow direction of the medium to be filtered, such that during filtration, the medium to be filtered flows in its flow direction from the pre-chamber (22, 23) in the housing (12) through the first filter (18, 19) into the gap (23, 24) between the first filter (18, 19) and the second filter (19, 20), and flows forward through the second filter (19, 20) to the outlet (16). The housing (12) has pre-chamber channels (44, 45) for supplying test fluid into the pre-chamber (22, 23), and gap channels (45, 46) for supplying the test fluid into the gap (23, 24). A connecting line (48) for fluid connection between the anterior chamber (22, 23) and the void (23, 24) is provided between the anterior chamber passages (44, 45) and the void passages (45, 46), wherein at least the fluid connection to the void (23, 24) can be closed; The integrity status of the dual-filter capsule (10) shall be determined based on at least the following two test phases: -- The first testing phase includes: with the fluid connection between the connecting line (48) and the gaps (23, 24) closed, supplying the test fluid to the anterior chambers (22, 23) and performing a first integrity check; and -- The second testing phase includes: while the anterior chambers (22, 23) are fluidly connected to the gaps (23, 24) via the connecting line (48), the test fluid is simultaneously supplied to the anterior chambers (22, 23) and to the gaps (23, 24) via the gap channels (45, 46), so that pressure equalization occurs between the anterior chambers (22, 23) and the gaps (23, 24), and a second integrity check is performed.
2. The method of claim 1, wherein the test fluid is a test gas, and wherein the method comprises wetting the first filter (18, 19) and / or the second filter (19, 20) with a wetting medium before determining the integrity status of the dual filter capsule (10).
3. The method of claim 1 or 2, wherein the first integrity check and / or the second integrity check includes one or more of the following testing procedures: Bubble point test; Diffusion test; Pressure holding test.
4. The method of claim 1, wherein the first test phase is performed in a dynamic mode, wherein the first integrity check is performed within such a short time after the test fluid is supplied to the pre-chamber (22, 23) or after the pressure of the test fluid in the pre-chamber (22, 23) is established, such that the time is shorter than the ratio of the volume of compressible gas in the gap (23, 24) to the target flow rate of the test fluid passing through the first filter (18) during the first integrity check.
5. The method of claim 1, wherein the first test phase is performed in a static mode, wherein during the first integrity check, the amount of test fluid continuously supplied via the anterior chamber passages (44, 45) is the same as the amount of test fluid that passes through the first filter (18, 19) and the second filter (19, 20) to exit via the outlet (16).
6. The method of claim 1, wherein pressurized fluid is supplied to the anterior chamber (22, 23) and / or the cavities (23, 24) via a sterile filter.
7. The method of claim 1, wherein the first filter (18, 19) and the second filter (19, 20) are arranged or will be arranged in the housing (12) as filter candles such that, during filtration, the medium to be filtered passes through the respective filter membranes of the first (18, 19) and the second filter (19, 20) in its flow direction, flowing substantially radially from the outside to the inside: Basically a cylindrical barrel-shaped core (26); A filter structure (28) surrounding the core (26) and having a filter membrane; and A substantially cylindrical barrel-shaped outer shell surrounding the filter structure (28) and the core (26).
8. The method of claim 1, wherein the first (18, 19) and / or the second filter (19, 20) comprises a pleated filter structure.
9. The method of claim 1, wherein the first filter (18, 19) comprises a first filter membrane having pores, and the second filter (19, 20) comprises a second filter membrane having pores, such that the pore size of the first filter membrane is larger than the pore size of the second filter membrane.
10. The method of claim 9, wherein The pore size of the first filter membrane has a value in the range of 0.3 μm to 0.6 μm; and The pore size of the second filter membrane has a value in the range of 0.1 μm to 0.3 μm.
11. The method of claim 10, wherein the pore size of the second filter membrane has a value in the range of 0.1 μm to 0.2 μm.
12. The method of claim 1, wherein the first filter (18, 19) comprises a porous first filter membrane, and the second filter (19, 20) comprises a porous second filter membrane, such that the pore size of the first filter membrane and the pore size of the second filter membrane have values in the range of 0.05 μm to 0.4 μm.
13. The method of claim 12, wherein the pore size of the first filter membrane and the pore size of the second filter membrane have values in the range of 0.1 μm to 0.2 μm.
14. The method of claim 1, wherein the dual filter capsule (10) is provided such that the housing (12) also has an inlet (14) for supplying the medium to be filtered into the pre-chamber (22, 23).
15. Systems used for integrity testing, including: A dual-filter capsule (10) having a housing (12) wherein a first filter (18, 19) and a second filter (19, 20) are arranged one after another in the flow direction of the medium to be filtered, such that during filtration, the medium to be filtered flows in its flow direction from the pre-chamber (22, 23) in the housing (12) through the first filter (18, 19) into the gap (23, 24) between the first filter (18, 19) and the second filter (19, 20), and flows forward through the second filter (19, 20) to the outlet (16). The housing (12) has pre-chamber channels (44, 45) for supplying test fluid into the pre-chamber (22, 23), and gap channels (45, 46) for supplying the test fluid into the gap (23, 24); and A connecting line (48) between the anterior chamber passages (44, 45) and the gap passages (45, 46) for fluid connection between the anterior chambers (22, 23) and the gaps (23, 24), wherein at least the fluid connection to the gaps (23, 24) can be closed; The integrity inspection device is designed to perform the following two test phases and determine the integrity status of the dual-filter capsule (10) based on them: -- The first testing phase includes: with the fluid connection between the connecting line (48) and the gaps (23, 24) closed, supplying the test fluid to the anterior chambers (22, 23) and performing a first integrity check; and -- The second testing phase includes: while the anterior chambers (22, 23) are fluidly connected to the gaps (23, 24) via the connecting line (48), the test fluid is simultaneously supplied to the anterior chambers (22, 23) and to the gaps (23, 24) via the gap channels (45, 46), so that pressure equalization occurs between the anterior chambers (22, 23) and the gaps (23, 24), and a second integrity check is performed.
Citation Information
Patent Citations
Method for testing integrity of filter media
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