Apparatus and method for producing solutions

Abstract

The invention relates to a device and a method for producing a solution consisting of at least one liquid first medium and at least one further second medium. The device comprises a first container for a liquid first medium and a second container for a second medium, each container being connected to an inlet of a static mixer via a pump which can be controlled by a process controller, and a sensor device which is arranged downstream of the static mixer in the flow direction and is connected to the process controller. The invention relates to a process control device for a sterile filter, comprising a static mixer and a flow divider valve which is arranged downstream of the static mixer in the flow direction and which can likewise be controlled by the process control device, the sterile filter being arranged downstream of the static mixer in the flow direction, the sterile filter having an RFID tag, and the RFID tag storing process-related data which can be read at least by the process control device.

Description

[0001] This divisional application is a divisional application of a Chinese patent application with the PCT application number PCT / EP2016 / 001455, national application number 201680044668.3, and invention title "Device and Method for Manufacturing a Solution", which was filed on August 29, 2016 and entered the Chinese national phase on January 30, 2018. Technical Field

[0002] The present invention relates to a device and a method for manufacturing a solution composed of at least one liquid first medium and at least one additional second medium. The device has a first container for the liquid first medium and a second container for the second medium, wherein the containers are each connected via a pump adjustable by a process controller to an inlet section of a static mixer. The device further has a sensing device disposed downstream of the static mixer in the liquid flow direction and connected to the process controller, and a diverter valve disposed downstream of the static mixer in the liquid flow direction and also capable controlled by the process controller.

[0003] The present invention also relates to a method for manufacturing a solution composed of at least one liquid first medium and at least one additional second medium when using the device according to any one of claims 1 to 10. Background Art

[0004] A static mixer is generally a tube or a channel with stationary inserts, which cause the mixing of the product flow of the fluid by utilizing the flow energy. Compared with a mixer with a movable tube mechanism, a static mixer generally has a smaller chamber volume and a very small power requirement. A static mixer is a closed system that requires neither maintenance nor inerting. In the case of a static mixer, the risk of proportional increase is very small due to the strongly defined geometry and flow guidance.

[0005] In current industrial applications, static mixers are often used. In addition, the fields of use of static mixers are very extensive: mixing pumpable liquids, dispersing and emulsifying immiscible components, mixing and homogenizing plastic melts, gas / liquid or liquid / liquid contact, material transport, heat transfer, and chemical reactions are all fields of use of static mixer technology.

[0006] An apparatus and a method for producing a solution composed of a liquid first medium and a second medium are known from JP 2013 / 07 1034 A1. A first container for the liquid first medium and a second container for the second medium are each connected via pumps adjustable by a process controller to an inlet section of a static mixer. Downstream in the direction of the liquid flow, the static mixer is connected to a sensing device for measuring density, which is connected to the process controller. A diverter valve controllable by the process controller is downstream of the sensing device in the direction of the liquid flow.

[0007] Here, the disadvantage is that the safety of producing a sterile solution of a defined composition from at least two different media is not sufficiently guaranteed.

[0008] Furthermore, a filtration device is known from DE 101 65 007 B4, which includes a filter with an RFID tag for improving the safety of the filtration process. SUMMARY OF THE INVENTION

[0009] The object of the present invention is to provide an apparatus and a method by which a sterile solution of a defined composition can be produced from at least two different media with high safety.

[0010] The object in terms of the apparatus is solved in the following way in combination with the features of the preamble of claim 1, namely that a sterile filter is downstream of the static mixer in the direction of the liquid flow, the sterile filter has an RFID tag, and the RFID tag stores process-related data, and the process-related data can be read at least by the process controller.

[0011] Since the sterile filter is downstream of the static mixer in the direction of the liquid flow, it is ensured that the produced solution is a sterile solution. Since the sterile filter has an RFID tag that stores process-related data that can be read at least by the process controller, the user can already implement process control during the preparation phase and errors can be avoided. Here, the process-related data refers to data that relates to the identity of the filter, the approval status, the compatibility with the buffer solution, and the test data.

[0012] By means of a sensing device downstream of the static mixer in the direction of the liquid flow and its connection to the process controller, the adjusted mixing ratio can be controlled and regulated by manipulating the pumps. By means of a diverter valve controllable by the process controller, in particular, the diverter valve can be opened in the case where the mixing ratio exceeds a limit value and the solution to be discarded can be discharged.

[0013] Preferred embodiments are the subject matter of the dependent claims.

[0014] According to another embodiment of the present invention, a third container for a third medium is connected to the inlet part of a static mixer by a pump that can be regulated by a process controller. Thereby, mixing the third solution component into the solution to be mixed is achieved relatively simply and safely. In order to improve the control of the mixing ratio to be produced, the sensing device can be extended here by adding another parameter to be measured.

[0015] According to another preferred embodiment of the present invention, the containers each also have an RFID tag that can be read at least by the process controller, in which other process-related data is stored. Thereby, further enhanced security is obtained for the process control performed in the preparation stage. It is particularly feasible to identify the containers and check their content regarding compatibility and approval, so that errors can be avoided.

[0016] According to another preferred embodiment of the present invention, the sensing device is arranged between the static mixer and the sterile filter. A controllable diversion valve can be arranged here between the sensing device and the sterile filter. As long as the sensing device is downstream of the sterile filter in the direction of the liquid flow, the controllable diversion valve is also downstream of the sensing device in the direction of the liquid flow.

[0017] According to another preferred embodiment of the present invention, the diversion valve is connected to a diversion line for diverting the solution with insufficient quality. In principle, it is applicable that the controllable diversion valve is always downstream of the sensing device in the direction of the liquid flow, in order to ensure the inspection before the diversion valve. Here, the diversion line is connected via a controllable second diversion valve to a return line leading to the first container. It is feasible to produce the necessary mixing ratio during the correction process in the case of correspondingly correcting the components to be transported.

[0018] According to another preferred embodiment of the present invention, the static mixer, the sensing device, and the sterile filter with an RFID tag form a pre-assembled mixing system, the connectors of which for connection to the container or to the pump assigned to the container are sterile connectors known to those skilled in the art. For this purpose, it is feasible that the pre-assembled mixing system is used as a disposable system for continuously producing process media, in particular for chromatography, cross-flow filtration, fermentation, and cell culture. By using disposable technology (also for the subsequent containers, the so-called disposable bags), the user is spared the troublesome cleaning steps and the corresponding confirmations as well as the associated high acquisition costs. In addition, the product space planning can be designed more flexibly by dispensing with rigid stainless steel components. By means of aseptic process management, the contamination risk due to mass-producing sterile mixing systems is reduced.

[0019] The problem in terms of the method is solved in the following way in combination with the preamble of claim 11, namely, the following steps are carried out:

[0020] a) Reading and verifying process-related data in the data stored in one or more RFID tags by a process controller,

[0021] b) Approving and starting the mixing process,

[0022] c) Monitoring mixing parameters by a sensing device and adjusting the mixing ratio via a pump by the process controller,

[0023] d) Approving the solution in the case of sufficient quality, or

[0024] e) Diverting the solution into a diversion line via a diverter valve in the case of insufficient quality.

[0025] By the method according to the invention, a sterile final fluid of defined composition is produced from at least two different liquids with high safety as a solution. The method according to the invention in particular has the features and advantages already described in the above device.

[0026] According to a preferred embodiment of the invention, in the case of insufficient quality, the solution from the diversion line is conveyed back via a return line to the first container for the first liquid medium in step f). What is achieved hereby is that the solution that has been discarded still reaches the desired quality. In principle, it is also possible that the solution from the diversion line is conveyed back via a return line to an additional container, which is likewise connected to the pre-assembled mixing system. Description of the Drawings

[0027] Other features and advantages of the invention result from the following detailed description and the drawings. Among them:

[0028] Figure 1 A schematic diagram of a device showing the first and second containers and a sensing device arranged between a static mixer and a sterile filter;

[0029] Figure 2 Showing corresponding to Figure 1 A schematic diagram of the device, however with a third container for a third medium;

[0030] Figure 3 Showing corresponding to Figure 2 A schematic diagram of the device, where the containers each have an RFID tag;

[0031] Figure 4 Showing corresponding to Figure 3 A schematic diagram of another device, however with a controllable second diverter valve and with a return line leading to the first container, where the first diverter valve is arranged between the sensing device and the sterile filter;

[0032] Figure 5 Showing corresponding to Figure 4Schematic diagram of another device, wherein the sensing device and the diverter valve are disposed downstream of the sterile filter in the direction of the liquid flow;

[0033] Figure 6 showing corresponding to Figure 3 Another schematic diagram of a device with a diverter valve arranged between the sensing device and the sterile filter; and

[0034] Figure 7 showing Figure 1 A schematic diagram of a mixer, a sensing device, and a sterile filter as a pre-assembled mixing system. Detailed Description

[0035] The device 1 for manufacturing a solution composed of at least one liquid first medium and at least one additional second medium mainly consists of a first container 2, a second container 3, a first pump 4, a second pump 5, a process controller 6, and a pre-assembled mixing system 7.

[0036] The first container 2 filled with the liquid first medium is connected to the first pump 4 arranged upstream in the direction of the liquid flow. Correspondingly, the second container 3 is connected to the second pump 5 arranged upstream of it in the direction of the liquid flow. The pumps 4, 5 are connected to the process controller 6 via a control line 8.

[0037] Corresponding to Figure 1 and 7 In the embodiment, the mixing system 7 includes a static mixer 9, a sensing device 10 arranged downstream of the mixer 9 in the direction of the liquid flow, and a sterile filter 11 arranged downstream of the static mixer 9 in the direction of the liquid flow.

[0038] The static mixer 9 has an inlet part 12 and an outlet part 13. The sensing device 10 is arranged between the static mixer 9 and the sterile filter 11 corresponding to Figure 1 and 7 in the embodiment and corresponding to Figure 3 in the embodiment. The sensing device 10 may have one or more sensors not shown here. Various parameters can be determined by using the sensing device 10. For example, conductivity or pH value can be determined by the sensing device 10. A pressure sensor or a volume sensor can also be provided. The sensing device 10 is connected to the process controller 6 via a signal line 14.

[0039] The sterile filter 11 includes an RFID tag 15 with a storage section (not shown) that can be read by the process controller 6. In the storage section of the RFID tag 15, process-related data (filter identity, approval status, compatibility with the buffer solution, and inspection data) is stored and can be read wirelessly by the process controller 6. The mixing system 7 has a known sterile connector 16 at its connection end for making a sterile connection. The mixing system 7 has a diverter valve 17 for discharging the discarded solution, and the diverter valve 17 is connected to the process controller 6 via another control line 18 and is controlled by the process controller 6.

[0040] Corresponding to Figures 2 to 6 the embodiment, in addition to the first container 2 and the second container 3, a third container 19 for a third medium is provided. Accordingly, the third pump 20 is placed upstream of the third container 19 in the liquid flow direction.

[0041] In Figure 3 the embodiment, the mixing system 7' corresponds to Figure 2 the mixing system 7 of the embodiment. The containers 2'', 3'' and 19'' have RFID tags 21 that can also be read by the process controller 6.

[0042] Other process-related data related to the containers 2'', 3'' and 19'' is stored in the RFID tags 21. In particular, it is possible to identify the containers and check their compatibility and approval status.

[0043] In Figure 4 the embodiment, the device 1''' has a reflux line 22 that connects the diversion line 23 of the diverter valve 17 to the container 2''' via a second diverter valve 24. Corresponding to Figure 4 the embodiment, the diverter valve 17 is arranged between the sensing device 10 and the sterile filter 11.

[0044] Figure 5 The embodiment of the device 1'''' basically corresponds to Figure 4 the embodiment, however, the sensing device 10 is arranged downstream of the sterile filter 11 in the liquid flow direction. Accordingly, the diverter valve 17 is arranged downstream of the sensing device 10 in the liquid flow direction.

[0045] Finally, Figure 6 the embodiment basically corresponds to Figure 3 the embodiment, however, the diverter valve 17 is arranged between the sensing device 10 and the sterile filter 11.

[0046] Corresponding to Figure 7In an embodiment, the static mixer 9, the sensing device 10 and the sterile filter 11 with an RFID tag 15 together with the sterile connector 16, which serves as a connector for connecting the containers 2, 3 or for connecting the pumps 4, 5 assigned to the containers 2, 3, form a pre-assembled mixing system 7.

[0047] Obviously, the embodiments discussed in the specific description and shown in the drawings are only exemplary embodiments of the present invention. Under the inspiration of the disclosure text of the present invention, a wide range of variant solutions are possible for those skilled in the art.

[0048] List of reference signs:

[0049] 1,1',1'',1''',1'''' equipment 2,2'',2''' first container 3,3'' second container 4 first pump 5 second pump 6 process controller 7,7' mixing system 8 control line 9 static mixer of 7 10 sensing device of 7 11 sterile filter of 7 12 introduction part of 9 13 export part 14 signal line of 10 15 RFID tag of 11 16 sterile connector 17 shunt valve 18 control line 19,19'' third container 20 third pump 21 RFID tag of 2'', 3'', 20'' 22 reflux line 23 shunt line of 17 24 second shunt valve

Claims

1. An apparatus (1, 1', 1'', 1''', 1'''') for manufacturing a sterile solution composed of at least one liquid first medium and at least one additional second medium, the apparatus having a first container (2, 2'', 2''') for the liquid first medium and a second container (3, 3'') for the second medium, wherein, Containers (2, 2'', 2''', 3, 3'') are respectively connected to the inlet part (12) of a static mixer (9) via pumps (4, 5) that can be regulated by a process controller (6). The device also has a sensing device (10) that is placed downstream of the static mixer (9) in the liquid flow direction, is connected to the process controller (6), and determines the parameters of the mixed solution, and has a diverter valve (17) that is placed downstream of the static mixer (9) in the liquid flow direction. Among them, a sterile filter (11) for aseptic filtration of the solution is placed downstream of the static mixer (9) in the liquid flow direction. It is characterized in that the diverter valve (17) is also controlled by the process controller (6) and is connected to a diversion line (23). the sterile filter (11) has an RFID tag (15). The RFID tag (15) stores process-related data, and the process-related data can be read at least by the process controller (6). Among them, the process-related data of the sterile filter includes the identity of the filter, the approval status, the compatibility with the buffer solution, or the inspection data. The containers (2, 2'', 2''', 3, 3'', 19, 19'') respectively have RFID tags (15) that can be read at least by the process controller (6), and other process-related data is stored in the RFID tags. The static mixer (9), the sensing device (10), and the sterile filter (11) with an RFID tag (15) form a pre-assembled mixing system (7, 7') as a disposable system for continuously manufacturing a process medium. The mixing system has a sterile connector (16) as a joint for connecting to the containers (2, 2'', 2''', 3, 3'', 19, 19'') or to the pumps (4, 5, 20) assigned to the containers (2, 2'', 2''', 3, 3'', 19, 19''), and a) By using the process-related data of the sterile filter and the determined parameters of the mixed solution, the process controller (6) controls and adjusts the adjusted mixing ratio by manipulating the pumps. And b) The process controller (6) is set to open the diverter valve when the mixing ratio exceeds a limit value, so as to divert the solution into the diversion line connected to the diverter valve. Thereby ensuring that the solution produced by the sterile filter is an aseptic solution.

2. The apparatus according to claim 1, characterized in that, The sensing device (10) has more than one sensor, and each sensor determines different parameters of the mixed solution to control the mixing ratio.

3. The apparatus according to claim 2, characterized in that, One of the more than one sensors is selected from the following group: Conductivity sensor; pH sensor; Pressure sensor; Volume sensor.

4. The apparatus according to claim 2, characterized in that, The multiple sensors are selected from the following group: Conductivity sensor; pH sensor; Pressure sensor; Volume sensor.

5. The apparatus according to any one of claims 1 to 4, characterized in that, The third containers (19, 19'') for the third medium are connected to the inlet part of the static mixer (9) via pumps (4, 5) that can be regulated by the process controller (6).

6. The apparatus according to any one of claims 1 to 5, characterized in that, The sensing device (10) is arranged between the static mixer (9) and the sterile filter (11), and the controllable diverter valve (17) is downstream of the sterile filter (11) in the direction of the liquid flow.

7. The apparatus according to any one of claims 1 to 5, It is characterized in that The sensing device (10) is arranged between the static mixer (9) and the sterile filter (11), and the controllable diverter valve (17) is arranged between the sensing device (10) and the sterile filter (11).

8. The device according to any one of claims 1 to 5, It is characterized in that The sensing device (10) is downstream of the sterile filter (11) in the direction of the liquid flow, and the controllable diverter valve (17) is downstream of the sensing device (10) in the direction of the liquid flow.

9. The device according to any one of claims 1 to 8, It is characterized in that The diversion line (23) is connected via a second diverter valve (24) to the return line (22) leading to the first container (2''') and / or an additional container.

10. The device according to any one of claims 1 to 9, It is characterized in that The first container (2) filled with a liquid first medium is connected to a first pump (4), and the first pump is located between the first container (2) and the inlet section (12) upstream of the static mixer in the direction of the liquid flow. And the second container (3) filled with a liquid second medium is connected to a second pump (5), and the second pump is either between the first container (2) and the first pump (4) or between the second container (3) and the inlet section (12) upstream of the static mixer in the direction of the liquid flow.

11. The device according to claim 10, It is characterized in that The first pump (4) is further located between the second pump (5) and the inlet section (12) upstream of the static mixer in the direction of the liquid flow.

12. A method for producing a solution composed of at least one liquid first medium and at least one further second medium when using the device (1, 1', 1'', 1''', 1'''') according to any one of claims 1 to 10, It is characterized in that Perform the following steps: a) Provide the device according to any one of claims 1 to 11. b) Read and check the process-related data in the data stored in one or more RFID tags (15, 21) by the process controller (6). c) Approve and start the mixing process. d) Monitor the mixing parameters by the sensing device (10) and adjust the mixing ratio by the process controller (6) via the pumps (4, 5, 20) using the process-related data of the sterile filter. e) Approve the solution in the case of sufficient quality, or f) In the case of insufficient quality, divert the solution into the diversion line (23) through the diverter valve (17).

13. The method according to claim 12, It is characterized in that In the case of insufficient quality, in step f), convey the solution from the diversion line (23) back to the first container (2, 2'', 2''') for the liquid first medium or an additional container via the return line (22).

Images