AUTOMATED DISPOSABLE FILTRATION DEVICE AND METHOD FOR CONTROLLING AN AUTOMATED DISPOSABLE FILTRATION DEVICE

Description

[0001] The invention relates to an automated disposable filtration device that is particularly suitable for large-volume filtration processes. The invention further relates to a method for controlling such an automated disposable filtration device.

[0002] In the field of single-use technology development for biopharmaceutical applications, filtration elements are enjoying increasing popularity and are now widely used. In recent years, for example, single-use filtration technologies have continuously evolved and are no longer used exclusively in laboratories and process development. Rather, single-use filtration elements are now also commonly used in commercial manufacturing processes for pharmaceutical products for clinical phases 1 to 3 (development stages in drug development) or in the commercial production of such active ingredients. Currently available single-use filtration devices are limited to smaller filter elements, which in turn are restricted to the pure "filtration" functionality.

[0003] WO 2017 / 032560 A1 discloses a fully pre-sterilizable, ready-to-connect, and integrity-testable disposable filtration device designed for large-volume filtration processes. This disposable filtration device comprises a plurality of disposable filter capsules of a standard size arranged in a predetermined grid and connected to each other by lines. The filter capsules are supported by a rigid holder.

[0004] WO 2016 / 177650 A1 discloses a modular system for the continuous, microbiologically reduced production or processing of a biopharmaceutical, biological macromolecular product from a heterogeneous cell culture fluid mixture. The system comprises the following modules: a filtration module, a chromatography module, an ultrafiltration module or diafiltration module, a dialysis module, and a module for continuous virus removal. The modular system is closed and microbiologically reduced. A special feature of the system is the possibility of automatic filter replacement under microbiologically reduced conditions. The completion of the venting of the new filter is detected on the unfiltered side by a pressure sensor, a fill level sensor, a scale, or a liquid detector.

[0005] However, with previous disposable filtration elements, the question of integration into automated processes was not considered. With the introduction of disposable filtration technology into commercial production, as described above, not only the scaling, i.e., the required filter size and thus the filtration area, but also the need for automated filtration processes is increasing. This requires the embedding of filtration elements in hose lines, plastic piping, disposable sensors, and connection systems, which can then be integrated into a holistic process solution only when connected to a suitable monitoring and control system.

[0006] In the field of disposable filtration technology, there is therefore a need for a ready-to-use disposable filtration device that enables a partially or fully automated filtration process on a large scale. The object of the invention is to meet this need.

[0007] This object is achieved by an automated disposable filtration device having the features of claim 1 and by a method for controlling an automated disposable filtration device having the features of claim 3. Advantageous and expedient embodiments of the device according to the invention and of the method according to the invention are specified in the associated subclaims.

[0008] The automated disposable filtration device according to the invention is intended for large-volume filtration processes and comprises an unfiltered material inlet, one or more filter elements (in one or more filter units), a filtrate outlet, a sterile air filter connected to a vent outlet of the disposable filtration device, sensors for detecting specific process parameters and control devices for adjusting specific process parameters, as well as an external monitoring and control system. The sensors and control devices are connected to the external monitoring and control system, which is configured to evaluate and process sensor data and to control the control devices based on one or more control algorithms.The sensors include a flow sensor located at the unfiltrate inlet, an inlet pressure sensor located at the unfiltrate inlet, an outlet fluid detector located at the filtrate outlet, and an outlet pressure sensor located at the filtrate outlet. The control devices include an inlet-side feed pump with adjustable flow rate, an inlet control valve located at the unfiltrate inlet, an outlet control valve located at the filtrate outlet, and a vent control valve inserted between the vent outlet and the sterile air filter. The vent control valve can be opened or closed directly by the external monitoring and control system.

[0009] The invention is based, among other things, on the realization that automation of a filtration process using disposable components is more important than in conventional reusable systems with stainless steel components due to the significantly higher material-related risks. Therefore, process reliability is even more important in disposable systems. Automation can reduce or even completely eliminate manual operator errors or settings. Should errors nevertheless occur or become apparent, they can be detected early. Furthermore, a significant increase in efficiency can be achieved through the continuous determination, control, monitoring, and adjustment of optimal process parameters.With the proposed disposable filtration device, it is possible to carry out a complete filtration process with all or at least some process steps partially or fully automatically using the monitoring and control system. This requires sensors and control devices connected to the monitoring and control system for recording, monitoring, and, if necessary, regulating certain process-relevant parameters.

[0010] The sensors and control devices connected to the monitoring and control system are all designed as disposable components.

[0011] The sensors preferably also comprise a vent fluid detector inserted between the vent outlet and the sterile air filter, which in turn is designed as a disposable component.

[0012] The invention also provides a method for controlling an automated disposable filtration device according to the invention, wherein the monitoring and control system carries out several or all of the following process steps at least partially automatically in succession: Filling the disposable filtration device with a wetting medium and completely venting it via the sterile air filter; rinsing and wetting the disposable filtration device or the filter element; emptying and venting the disposable filtration device by static emptying or actively by pressing it empty with the aid of a gaseous medium; pre-use filter integrity test with a gaseous medium; filling the disposable filtration device with a liquid product and completely venting it; filtration of a liquid product under permanent monitoring of the inlet pressure orOutlet pressure and preferably flow rate; filtration of a liquid product with interim venting of the disposable filtration device if necessary; expelling residual product liquid after completion of filtration and rinsing with buffer or water or another liquid medium; emptying and venting the disposable filtration device by static emptying or actively by forcing it empty using a gaseous medium; and post-use filter integrity testing with a gaseous medium.

[0013] Preferably, the process steps are carried out one after the other in the order mentioned within the framework of an overall process.

[0014] In the following, certain preferred control and regulation processes are specified which can advantageously be carried out fully or partially automatically within the framework of a filtration process during one or more of the above-mentioned process steps with the aid of the control and regulation system and the sensors or regulation devices connected to it.

[0015] The filling of the disposable filtration device with wetting medium and / or product takes place under continuous monitoring of the pressure at the inlet pressure sensor by the control and monitoring system. The control and monitoring system regulates the output of the feed pump so that a specified maximum pressure is not exceeded.

[0016] When venting and / or re-venting the disposable filtration device via the sterile air filter, the control system opens the vent control valve until the vent liquid detector detects liquid. The control system then immediately closes the vent control valve.

[0017] During the flushing and wetting of the disposable filtration device or filter element, the control system obtains information from the flow sensor at the unfiltered media inlet and regulates the feed pump's output based on this. At the same time, the control system continuously monitors the pressure at the inlet pressure sensor. The control system automatically sets and regulates the desired flushing performance and pressure ratios via the inlet control valve and / or the outlet control valve.

[0018] When flushing and wetting the disposable filtration device or filter element, the monitoring and control system regulates and / or cycles the vent control valve and the outlet control valve alternately so that a controlled mixing and / or displacement of one liquid by another liquid takes place.

[0019] When emptying and venting the disposable filtration device by static emptying or actively by emptying it with air, the control and monitoring system opens the vent control valve and / or the outlet control valve to allow the liquid to flow out.

[0020] When the disposable filtration device is emptied and vented by static emptying or actively by pressing it empty with air, the control and monitoring system signals that the emptying process is complete based on information from the output liquid detector.

[0021] During the pre-use filter integrity test with a gaseous medium, the control and monitoring system controls an external integrity test device, which performs the integrity test itself. The control and monitoring system uses a closing element (actuator) to control the control valves so that the inlet control valve is closed and the outlet control valve and the vent control valve are open.

[0022] During the filtration of a product and / or during the discharge of residual product liquid after filtration and rinsing with buffer or water, and / or during the emptying and venting of the disposable filtration device, the monitoring and control system continuously monitors the pressure at the inlet pressure sensor. Alternatively or additionally, the monitoring and control system obtains information from the flow sensor at the unfiltered product inlet. Based on this information, the monitoring and control system regulates the feed pump to ensure a specific filtration performance is achieved and / or that a predetermined pressure is not exceeded.

[0023] In the event of an excessive pressure increase, the monitoring and control system throttles or switches off the feed pump and / or closes the inlet control valve.

[0024] When product residual liquid is pushed out after filtration is completed, the control and monitoring system signals that the pushing out process is complete based on information from the output liquid detector.

[0025] Further features and advantages of the invention will become apparent from the following description and the accompanying drawings, to which reference is made. In the drawings: Figure 1 a perspective view of a disposable filtration device with connecting lines and other connecting elements; and Figure 2 a schematic side view of an automated disposable filtration device according to the invention.

[0026] In Figure 1A disposable filtration device 10 is shown, which is similar to the device known from WO 2017 / 032560 A1. A plurality of filter capsules 12 are held in position by a rigid holder 14 in a predetermined arrangement (grid). The term "filter capsule" is to be understood generally here and is intended to refer to any independently mountable assembly with one or more filter elements (membranes) installed in one or more filter units. The holder 14 comprises support columns 16, which are connected to one another by cross struts 18. Feet 20 ensure secure support of the device 10. Holding means 22 for the individual filter capsules 12 are provided on the cross struts 18. The filter capsules 12 are completely or at least largely connected to one another by rigid, pressure-resistant pipes 24.The specific route of the pipes 24 shown here as examples is determined by the intended operation of the filtration device (parallel or series connection of the filter capsules 12), whereby the pipes 24 have the necessary branches 26 to the individual filter capsules 12. Where necessary, the pipes 24 are attached to the holder 14. The essential components of the rigid holder 14, the rigid housings of the filter capsules 12 and the rigid pipes 24 are all preferably made of the same material. This material and any other materials used in the device 10 (e.g., for any flexible hose lines) are sterilizable, in particular by means of gamma radiation, and autoclavable. The disposable filtration device 10 can thus be sterilized in the pre-assembled, i.e., ready-to-connect state and then packaged or packaged and then sterilized.The disposable filtration device 10 is designed for a large-volume filtration process. In particular, the filter capsules 12 provide a sufficiently large filtration area for such a process.

[0027] In Figure 1Examples of lines, branches, and connections are shown that can be provided for the integration of certain sensors and control devices for automating the disposable filtration device 10. An inlet valve 28 is connected to an unfiltrate inlet of the rigid disposable filtration device 10 via a piece of hose. Upstream of the inlet valve 28, a branch 30 is provided, on one branch of which a Tri-Clamp connection 32 is provided, and on the other branch of which a reinforced intermediate hose section 34 and an inlet hose line 36 connected thereto with a first sterile connector 38 are provided. A filtrate outlet of the rigid disposable filtration device 10 is connected to an outlet valve 40 via a piece of hose.Downstream of the outlet valve 40, a branch 42 is provided, one of whose branch lines has a Tri-Clamp connection 44, and the other branch of which has a reinforced intermediate hose section 46 and an outlet hose line 48 connected thereto with a second sterile connector 50. A reinforced vent hose line 52 leads from a vent outlet of the disposable filtration device 10 to an air filter holder carrying a sterile air filter 54.

[0028] Based on the Figure 2The exemplary configuration of a disposable filtration device 10 shown in the figure illustrates the integration of sensors and control devices for automating the disposable filtration device 10. For the sake of clarity, not all components and line branches are intentionally shown. As already mentioned, hose connections (and possibly additional ones) are provided at an unfiltered material inlet 56, a filtrate outlet 58, and a vent outlet (or air inlet) 60 of the disposable filtration device 10 for the sensors and control devices described below, all of which are designed as disposable components.

[0029] A flow sensor 62 for determining the flowing volume per unit time, an inlet pressure sensor 64, and an inlet control valve 66 are provided at the unfiltrate inlet 56. An outlet fluid detector 68, an outlet control valve 70, and an outlet pressure sensor 72 are provided at the filtrate outlet 58. A vent control valve 74 and a vent fluid detector 76 are provided at the vent outlet 60.

[0030] A fundamental prerequisite for complete or partial (individual process steps) automation of the disposable filtration device 10 is that the integrated sensors and control devices are connected to a monitoring and control system 78 via electrical lines, thus enabling control of the entire process or the respective process step. The electrical lines serve, on the one hand, to operate the sensors and control devices and, on the other hand, where provided, to transmit and / or receive data or signals required for monitoring and / or control. Alternatively, the data or signal transmission can also be carried out wirelessly.The control and monitoring system 78 is not a disposable component, but rather an electronic system located remotely from the filter capsules 12, which contains suitable software and hardware for evaluating and processing sensor data and for controlling the control devices based on one or more control algorithms.

[0031] The following describes an example of a filtration process that can be carried out with the disposable filtration device 10, which is divided into the following fully or partially automated individual steps: 1) Filling the disposable filtration device 10 with a wetting medium (e.g. water) and completely venting it via the sterile air filter 54; 2) Rinsing and wetting the entire disposable filtration device 10 or the filter element (filtration-effective layer); 3) Emptying and venting the disposable filtration device 10 by static emptying or actively by pressing it empty with air; 4) Pre-use filter integrity test with a gaseous medium, e.g. air; 5) Filling the disposable filtration device 10 with product and completely venting it (process as in step 1); 6) Filtration of the product under permanent monitoring and, if necessary, checking the inlet pressure oroutlet pressure; 7) filtration of the product with intermittent venting if necessary; 8) expelling residual product liquid after filtration to reduce losses and rinsing with buffer or water; 9) emptying and venting the disposable filtration device 10 by static emptying or actively by forcing it empty with air (as in step 3); and 10) post-use filter integrity test with a gaseous medium, e.g., air (process as in step 4).

[0032] Regarding step 1: When filling the disposable filtration device 10 with a wetting medium (e.g., water) using a feed pump 80 and completely venting via the sterile air filter 54, there are several possible errors that entail particularly high risks due to the disposable technology.

[0033] A primary risk is that the filling rate could be too high, leaving the air in the system with insufficient time to escape from the cavities and rise to the top. In this case, air can be released later in the filtration process, accumulating as air bubbles in the upper part of the system, thus negatively impacting the filtration area and thus the filter efficiency.

[0034] The automatic control of this process step provides for the filling of the disposable filtration device 10 to take place while continuously measuring and monitoring the pressure at the inlet pressure sensor 64. The monitoring and control system 78 ensures, in particular, that the feed pump 80 initially starts slowly to ensure a moderate filling process while not exceeding the permissible maximum pressure.

[0035] A second risk occurs primarily at the end of the filling process, when the operator of the disposable filtration device 10 fails to recognize, or recognizes too late, the moment when the wetting medium reaches the upper level and penetrates the vent hose line 52, causing the wetting medium to penetrate the sterile air filter 54. In this case, there is a risk that the sterile air filter 54 will become wetted and thus have no or only limited air permeability, and thus can no longer fulfill its intended function, namely to allow the air to escape from the system in a sterile manner, or can only fulfill it to a limited extent.

[0036] By using the vent control valve 74, followed by the vent liquid detector 76 at the outlet of the vent hose line 52, between the filter capsules 12 and the sterile air filter 54, the monitoring and control system 78 allows for controlled and slow venting by slightly opening the vent control valve 74. As soon as the liquid level reaches the upper area of the disposable filtration device 10 and the liquid penetrates the ascending vent hose line 52, the vent liquid detector 76 detects this, and the monitoring and control system 78 immediately transmits a signal to the vent control valve 74, which is immediately closed before the liquid reaches the sterile air filter 54.

[0037] A third risk is that with manual pinch valves it may well happen that the operator activates the feed pump 80 but at that time has not opened a manually operated valve at the pump outlet or has not opened it fully, or the inlet hose line 36 is kinked at one point, which would very quickly cause overpressure in the hose system, which could cause the hose system or a hose connection to burst or cause a leak. Such a risk is particularly important to consider given the limited and often inconsistent pressure resistance of plastic hose sets and transfer or bag systems. Aside from the risk of microbiological contamination, a leak can also pose a significant health and economic risk depending on the product and process step.

[0038] Thanks to the automatically controlled filling process, the speed of the feed pump 80 and thus the flow rate can be monitored and controlled by the monitoring and control system 78. The inlet pressure sensor 64 can monitor the maximum permissible pressure of the disposable filtration device 10 and, if necessary, adjust the pump output or even stop the feed pump 80 completely if, for example, a hose line is blocked and the maximum permissible pressure is reached.

[0039] Regarding step 2: Even when rinsing and wetting the entire disposable filtration device 10 or the filter element (filtration-effective layer), errors can be made during manual operation. Without appropriate sensor technology, these errors can only be avoided with some degree of certainty with the aid of other tools. The rinsing process serves to wash out undesirable components and to condition and thus prepare the filter elements in the filter capsules 12 for the subsequent filtration process. Both the amount of rinsing medium and the flow rate are important.

[0040] The first risk in this process step is that the flushing volume combined with the flushing capacity or the recommended pressure conditions are not adhered to, resulting in the filter unit not being flushed and prepared optimally. Manufacturers of the filter capsules often specify what these process conditions should be. For example, in addition to the flow rate, a certain pressure difference between the inlet and outlet pressure can be helpful or even necessary in this process step.

[0041] With the help of the monitoring and control system 78, which receives information from the flow sensor 62 at the unfiltered media inlet 56 of the disposable filtration device 10, the fluid flow can be controlled via the speed of the feed pump 80. At the same time, the desired rinsing capacity can be set and regulated with the inlet control valve 66 while continuously measuring the desired pressure conditions.

[0042] A second risk in this process step is due to the fact that, due to the fluid dynamics within the disposable filtration device 10, the rinsing and displacement of one medium (e.g., rinse water) with another medium (e.g., product) can take a relatively long time and cause significant mixing phases during the transition from filter wetting to filtration. This can lead to high consumption of rinsing solution, and the loss of product can also be very significant, which represents an economic risk. In manual operation, the user of a disposable filtration device 10 cannot control and reproducibly create the conditions required to avoid this risk.

[0043] Thanks to the control and monitoring system 78, a precisely predefined, e.g. alternating, timing of the vent control valve 74 and the outlet control valve 70 can be set in order to achieve and ensure optimal mixing or displacement of one liquid by another liquid under controlled conditions.

[0044] Regarding step 3: Emptying and venting the disposable filtration device 10 by static emptying or actively by emptying with the aid of air requires the vent control valve 74 and / or the inlet control valve 66 to be fully opened to ensure that air can enter the disposable filtration device 10 and the liquid can drain out of the filtrate outlet 58 located at the bottom due to gravity.

[0045] When performing this process step manually, the operator is unable to determine whether the static draining is sufficient because they cannot visually check the liquid level within the disposable filtration device 10. If the control valves 74 and 66 located above are not opened or are not opened sufficiently, the liquid may not drain or may not drain completely, and the disposable filtration device 10 may not drain completely.

[0046] For the automatic control of this process step, the output liquid detector 68 is included at the filtrate outlet 58 of the disposable filtration device 10. The output liquid detector 68 sends a signal to the monitoring and control system 78, which signals to the operator that the emptying process is complete and that there is no residual liquid in the lower part of the disposable filtration device 10, even though this may not be visually visible.

[0047] Regarding step 4: Before the intended filtration process, the filter elements are typically subjected to an integrity test with a gaseous medium, especially air. The integrity test is performed, for example, with the inlet control valve 66 completely closed via the vent outlet or air inlet 60. The inlet side of the disposable filtration device 10 is subjected to a defined test pressure, generated by an externally connected integration test device, to subsequently check whether and for how long this test pressure can be maintained. This duration allows conclusions to be drawn about the integrity of the filter membranes.

[0048] If this process step is performed manually, there is a risk that the operator of the disposable filtration device 10 may not have closed the inlet control valve 66 or may not have closed it sufficiently tightly, allowing small amounts of air to escape during the test phase and influence the test result. This would lead to an incorrect test result, requiring the integrity test and possibly the entire rinsing step prior to the integrity test to be repeated. This would require a significant additional time expenditure.

[0049] The control and monitoring system 78 enables the automatic and reliable closure of the inlet control valve 66 (as well as the other control valves 70, 74) with an electric or pneumatic actuator, which closes a closing body along a predefined path and with a defined and controlled force. The risk of the inlet control valve 66 being closed incompletely or too weakly by the operator is thus eliminated.

[0050] Regarding step 5: The risks associated with filling the disposable filtration device 10 with product and completely venting it correspond to those already described in connection with step 1. Therefore, please refer to the explanations therein regarding the avoidance or minimization of these risks.

[0051] Regarding step 6: The filtration of the product should generally be carried out under constant flow conditions, with permanent monitoring and, if necessary, control of the inlet and outlet pressure.

[0052] Typically, a disposable filtration device 10 has a limited capacity depending on the filter area and product. This means that after a certain amount of filtration, the filter pores gradually begin to clog, which leads to an increase in the inlet pressure at a constant flow rate. However, this pressure is limited by the pressure limitation of the disposable filtration device 10 and must not be exceeded to prevent the disposable filtration device 10 from bursting or leaking. In manual processes, the pressure must therefore be continuously monitored and controlled by the operator.

[0053] The automated disposable filtration device 10, equipped with the inlet pressure sensor 64 at the unfiltered media inlet 56, allows for continuous and seamless pressure monitoring with the aid of the monitoring and control system 78. If a pressure increase occurs, a critical overpressure situation can be avoided by throttling or shutting off the feed pump 80 and / or closing the inlet control valve 66.

[0054] Regarding step 7: Filtration of the product, with occasional venting if necessary, is also prone to errors when performed manually. Firstly, it is important to maintain the correct filtration pressure; secondly, certain flow rates must not be exceeded, for example, to protect the product from excessive shear forces or prevent premature blockage. Furthermore, if venting is performed incorrectly, there is a risk that the sterile air filter 54 could become wetted, thus impairing its function.

[0055] With the help of the control and monitoring system 78, which receives information from the flow sensor 62 at the unfiltered material inlet 56 of the disposable filtration device 10, the desired filtration performance can be set and regulated via the speed of the feed pump 80. This ensures that the specified process parameters are adhered to as optimally as possible, ensuring that the entire filtration process runs as evenly and gently as possible.

[0056] Another risk in filtration arises towards the end of the filtration process. The pressure in the system can rise to critical levels if the filters become blocked, posing a risk of bursting, especially for the hoses. The risk of bursting can be further increased by improper handling.

[0057] The monitoring and control system 78 can reliably detect filter blockage by continuously monitoring pressure and flow. By appropriately controlling the speed of the feed pump 80 and the inlet control valve 66, the system can be shut down if the filters become blocked.

[0058] During filtration, air or gas can slowly accumulate and become trapped in the filter unit due to release from the liquid medium or due to process conditions. This can lead to the liquid level in the filter unit dropping and the upper area of the filter elements themselves no longer being effective in filtering. This reduces the effective filtration area and thus also the filter capacity, which represents an economic risk. The control and monitoring system 78 can automatically initiate interim re-venting steps to counteract this risk by continuously monitoring the liquid level with the aid of the vent liquid detector 76.

[0059] During the subsequent venting process itself, there is also a risk that medium can penetrate into the venting hose line 52 up to the sterile air filter 54 and then wet the sterile air filter 54. After that, venting of the system is only possible to a limited extent, or possibly not at all.

[0060] By using the vent control valve 74, followed by the vent liquid detector 76 at the outlet of the vent hose line 52, between the filter capsules 12 and the sterile air filter 54, the monitoring and control system 78 allows for controlled and slow venting by slightly opening the vent control valve 74. As soon as the liquid level reaches the upper area of the disposable filtration device 10 and the liquid penetrates the ascending vent hose line 52, the vent liquid detector 76 detects this, and the monitoring and control system 78 immediately transmits a signal to the vent control valve 74, which is immediately closed before the liquid reaches the sterile air filter 54.

[0061] Regarding step 8: When pushing out residual product liquid after completion of filtration and rinsing with buffer or water, there is a risk, among other things, that the pressure in the system will rise to a high level after the residual product liquid has been successfully pushed out, since the wetted filters are not permeable to air.

[0062] By incorporating the inlet pressure sensor 64, the monitoring and control system 78 can throttle the output of the feed pump 80 early and, if necessary, shut it down if the pressure becomes too high. Furthermore, it is possible to regulate the pressure via the vent control valve 74. At the same time, the output liquid detector 68 at the filtrate outlet 58 ensures efficient use of the residual product liquid, since the system detects when all the residual liquid has been expelled, meaning no further liquid is expelled.

[0063] During subsequent rinsing, the system must be vented again, which again carries the risk of contaminating the sterile air filter 54. Afterward, venting the system is only possible to a limited extent, or possibly not at all.

[0064] By using the vent control valve 74, followed by the vent liquid detector 76 at the outlet of the vent hose line 52, between the filter capsules 12 and the sterile air filter 54, the monitoring and control system 78 allows for controlled and slow venting by slightly opening the vent control valve 74. As soon as the liquid level reaches the upper area of the disposable filtration device 10 and the liquid penetrates the ascending vent hose line 52, the vent liquid detector 76 detects this, and the monitoring and control system 78 immediately transmits a signal to the vent control valve 74, which is immediately closed before the liquid reaches the sterile air filter 54.

[0065] Regarding step 9: When emptying and venting the disposable filtration device 10 by static emptying or actively by pressing it empty with air, there is a risk that the system cannot be safely statically emptied if the vent control valve 74 and / or the inlet control valve 66 are not open. It is generally difficult to determine the current degree of emptying of the system because it is not readily visible to the operator how much residual fluid is still in the system.

[0066] For automatic control of this process step, the vent control valve 74 and / or the inlet control valve 66 and the outlet liquid detector 68 are included at the filtrate outlet 58 of the disposable filtration device 10. The vent control valve 74 and / or the inlet control valve 66 are automatically opened, and the outlet liquid detector 68 can reliably detect whether the disposable filtration device 10 has completely emptied itself. Furthermore, the outlet liquid detector 68 can detect the successful completion of the emptying process and terminate the process step.

[0067] If the system is actively emptied with air via the inlet line, there is a risk that the pressure will rise sharply after the liquid has been successfully expelled, as the wetted membrane is impermeable to air. To avoid the risk of bursting, the pressure is continuously monitored using the inlet pressure sensor 64 at the unfiltered inlet 56 and the monitoring and control system 78. If a pressure increase occurs, a critical overpressure situation can be avoided by throttling or shutting off the feed pump 80 or by closing the inlet control valve 66.

[0068] Of course, further and / or different sensors and control devices than those explained above can be provided for the (partially) automated execution of the above-explained and / or additional or different processes or process steps. List of reference symbols

[0069] 10 Disposable filtration device 12 Filter capsule 14 Bracket 16 Support column 18 Cross brace 20 Stand 22 Holding device 24 Pipeline 26 Branch 28 Inlet valve 30 Branch 32 Tri-Clamp connection 34 Intermediate hose section 36 Inlet hose line 38 First sterile connector 40 Outlet valve 42 Branch 44 Tri-Clamp connection 46 Intermediate hose section 48 Outlet hose line 50 Second sterile connector 52 Vent hose line 54 Sterile air filter 56 Unfiltered liquid inlet 58 Filtrate outlet 60 Vent outlet 62 Flow sensor 64 Inlet pressure sensor 66 Inlet control valve 68 Outlet liquid detector 70 Outlet control valve 72 Outlet pressure sensor 74 Vent control valve 76 Vent liquid detector 78 Monitoring and control system 80 Feed pump

Claims

1. Automated single-use filtration device (10) for large-volume filtration processes, comprising an unfiltrate inlet (56), one or more filter elements, a filtrate outlet (58), a sterile air filter (54) connected to a venting outlet (60) of the single-use filtration device (10), and sensors for detecting specific process parameters and regulating mechanisms for adjusting specific process parameters, as well as an external monitoring and control system (78), wherein the sensors and regulating mechanisms are connected to the external monitoring and control system (78) which is adapted for evaluating and processing sensor data and for controlling the regulating mechanisms based on one or more control algorithms, wherein the sensors comprise the following sensors: a flow sensor (62) arranged at the unfiltrate inlet (56); an inlet pressure sensor (64) arranged at the unfiltrate inlet (56); an outlet liquid detector (68) arranged at the filtrate outlet (58); an outlet pressure sensor (72) arranged at the filtrate outlet (58); wherein the regulating mechanisms comprise the following regulating mechanisms: an inlet-side feed pump (80), the delivery rate of which is adjustable; an inlet regulating valve (66) arranged at the unfiltrate inlet (56); an outlet regulating valve (70) arranged at the filtrate outlet (58); a venting regulating valve (74) inserted between the venting outlet (60) and the sterile air filter (54), wherein the venting regulating valve (74) can be immediately opened or closed by the external monitoring and control system (78).

2. Single-use filtration device (10) according to claim 1, characterized in that the sensors comprise a venting liquid detector (76) inserted between the venting outlet (60) and the sterile air filter (54).

3. Method of controlling an automated single-use filtration device according to any one of the preceding claims, wherein the monitoring and control system (78) performs, at least partially automatically, some or all of the following process steps one after the other: - filling the single-use filtration device (10) with a wetting medium and complete venting via the sterile air filter (54) ; - rinsing and wetting the single-use filtration device (10) or the filter element; - emptying and aerating the single-use filtration device (10) by static draining or actively by emptying by pressing with a gaseous medium; - pre-use filter integrity test using a gaseous medium; - filling the single-use filtration device (10) with a liquid product and complete venting; - filtering a liquid product under permanent supervision of the inlet pressure or outlet pressure and preferably of the flow rate; - filtering a liquid product under intermediate post-venting of the single-use filtration device (10) if required; - expelling residual product liquid after completion of the filtration and rinsing with buffer or water or another liquid medium; - emptying and aerating the single-use filtration device (10) by static draining or actively by emptying by pressing with a gaseous medium; and - post-use filter integrity test using a gaseous medium.

4. Method according to claim 3, characterized in that the filling of the single-use filtration device (10) with wetting medium and / or product is carried out under continuous supervision of the pressure at the inlet pressure sensor (64) by the monitoring and control system (78), and the monitoring and control system (78) regulates the performance of the feed pump (80) such that a predetermined maximum pressure is not exceeded.

5. Method according to claim 3 or 4, characterized in that, during venting and / or post-venting of the single-use filtration device (10) via the sterile air filter (54), the venting regulating valve (74) is opened by the monitoring and control system (78) until the venting liquid detector (76) detects liquid, and in that the monitoring and control system (78) then immediately closes the venting regulating valve (74).

6. Method according to any one of claims 3 to 5, characterized in that, during rinsing and wetting of the single-use filtration device (10) or of the filter element, the monitoring and control system (78) obtains information from the flow sensor (62) at the unfiltrate inlet (56) and regulates the performance of the feed pump (80) based thereon, wherein preferably the monitoring and control system (78) at the same time continuously supervises the pressure at the inlet pressure sensor (64) and adjusts and regulates a desired rinsing performance and desired pressure conditions via the inlet regulating valve (66) and / or the outlet regulating valve (70).

7. Method according to any one of claims 3 to 6, characterized in that, during rinsing and wetting of the single-use filtration device (10) or of the filter element, the monitoring and control system (78) regulates and / or clocks the venting regulating valve (74) and the outlet regulating valve (70) alternately, such that a controlled mixing and / or displacement of a liquid by another liquid takes place.

8. Method according to any one of claims 3 to 7, characterized in that, during emptying and aerating of the single-use filtration device (10) by static draining or actively by emptying by pressing with air, the monitoring and control system (78) opens the venting regulating valve (74) and / or the outlet regulating valve (70).

9. Method according to any one of claims 3 to 8, characterized in that, during emptying and aerating of the single-use filtration device (10) by static draining or actively by emptying by pressing with air, the monitoring and control system (78) signalizes that the emptying process is completed based on information from the outlet liquid detector (68).

10. Method according to any one of claims 3 to 9, characterized in that, during the pre-use filter integrity test using a gaseous medium, the monitoring and control system (78) pilots an external integrity test device which performs the integrity test itself, wherein the monitoring and control system (78) pilots the regulating valves via a closing body (drive) such that the inlet regulating valve (66) is closed and the outlet regulating valve (70) and the venting regulating valve (74) are open.

11. Method according to any one of claims 3 to 10, characterized in that, during the filtration of a product and / or the expelling of residual product liquid after completion of the filtration and rinsing with buffer or water and / or during emptying and aerating of the single-use filtration device (10), the monitoring and control system (78) continuously supervises the pressure at the inlet pressure sensor (64) and / or obtains information from the flow sensor (62) at the unfiltrate inlet (56), and in that, based thereon, the monitoring and control system (78) regulates the feed pump (80) such that a specific filtration performance is achieved and / or a predetermined pressure is not exceeded, wherein, in the event of an excessive pressure increase, the monitoring and control system (78) throttles the feed pump (80) or switches it off and / or closes the inlet regulating valve (66).

12. Method according to any one of claims 3 to 11, characterized in that, during expelling of residual product liquid after completion of the filtration, the monitoring and control system (78) signalizes that the expelling process is completed based on information from the outlet liquid detector (68).