Filter assembly, filter system and online integrity test method

Abstract

The invention discloses a filtering assembly, a filtering system and an on-line integrity testing method.The filtering assembly comprises a liquid module, a liquid outlet module, a main fluid filter and a main air filter located on the upstream of the main fluid filter, and the liquid outlet module is connected with a first waste discharge container in a sealed mode; the second waste discharge container is arranged at the first downstream end of the main air filter, and the interiors of the first waste discharge container and the second waste discharge container are isolated from the outside, so that the internal sealing performance of the filter assembly is improved; the first waste discharge container and the second waste discharge container can receive wetting liquid and test gas respectively, the wetting liquid and the test gas are prevented from being directly discharged into the environment, the sealing performance in the whole flow path and the sterile requirement of the use environment can be guaranteed, meanwhile, the wetting liquid and the test gas flow into the corresponding containers in the waste discharge module, and the waste discharge efficiency is improved. Endpoint indication of the wettability and integrity tester is also achieved.

Description

Technical Field

[0001] The present invention relates to the technical field of aseptic filtration technology, and in particular to a filtration component, a filtration system and an online integrity testing method. Background Art

[0002] With reference to the requirements of the Sterile Drug Appendix (Draft for Comment) of the Good Manufacturing Practice for Pharmaceuticals (Revised in 2010), each stage of sterile drug production (including the stages before sterilization) should take measures to reduce contamination by microorganisms, particulates, and bacterial endotoxins / pyrogens in accordance with the Contamination Control Strategy (CCS) for Sterile Drug Production. Depending on the production process, sterile drugs can be either terminally sterilized or non-terminally sterilized products.

[0003] For terminally sterilized products, packaging containers and equipment components should be cleaned using validated processes to ensure that microbial, particulate, and bacterial endotoxin / pyrogen contamination is adequately controlled. The interval between preparation and sterilization of the drug solution should be shortened as much as possible, and standards for controlling the interval from preparation to filling and sterilization should be established based on the product characteristics and storage conditions.

[0004] For non-terminally sterilized products, refer to Section 3 of the Appendix to Sterile Drugs (Draft for Comment) of the "Good Manufacturing Practice for Pharmaceuticals (Revised in 2010)" on "Sterile Filtration of Non-Terminally Sterilized Products". Aseptic operations should be minimized through engineering designs such as sterilization after complete assembly. Pipes and equipment that are in direct contact with the product should be sterilized online after assembly as much as possible. For the sterilization filtration process of non-terminally sterilized products, measures should be taken to reduce the risk of filtration sterilization. Sterile filter components should be sterilized before use and then undergo integrity testing. Gas filters used for sterilization of critical sterile gases (such as compressed air and nitrogen) should be integrity tested before being removed from the casing after use.

[0005] When the sterilizing filter is undergoing integrity testing, the wetting liquid used to wet the sterilizing filter and the original waste gas in the sterilizing filter will be discharged into the environment. During this process, the test gas or liquid may flow back and contaminate the sterilizing filter. Therefore, in the filtration process with higher sterility requirements, the actual use environment (Class C or Class B environment) and the entire filtration flow path need to take into account the sterility requirements, so it is necessary to improve the sealing requirements of the entire fluid filtration system. Summary of the Invention

[0006] In view of the shortcomings of the prior art, the purpose of the present invention is to provide a filter assembly, a filter system and an online integrity testing method, which solve the problem that the sterilizing filter in the prior art is easily contaminated by the outside world when discharging waste.

[0007] In order to achieve the above object, the present invention adopts the following technical solutions:

[0008] A filter assembly comprising a liquid inlet module, a liquid outlet module, a main fluid filter and a main air filter located upstream of the main fluid filter;

[0009] The main fluid filter includes a first upstream portion and a first downstream portion, the first downstream portion is sealedly connected to the liquid outlet module, and the main air filter includes a first upstream end and a first downstream end;

[0010] The invention also includes a waste discharge module, wherein the waste discharge module includes a first waste discharge container sealedly connected to the liquid outlet module and a second waste discharge container sealedly connected to the first downstream end of the main air filter;

[0011] The liquid inlet module is sealedly connected to both the first upstream portion and the first upstream end, and is capable of communicating with the main fluid filter or the main air filter. The liquid inlet module has a liquid inlet for connecting to a wetting liquid source or a feed liquid source;

[0012] The first upstream end and / or the first upstream portion has an interface capable of sealingly communicating with a filter integrity testing device or a container integrity testing device, so as to allow the test gas passing through the filter integrity testing device or the container integrity testing device to pass only through the main air filter, or only through the main fluid filter and then into the first waste container, or pass through the main air filter and the main fluid filter in sequence and then into the first waste container.

[0013] The filter assembly of the present invention is sealed and connected to the main air filter upstream of the main fluid filter in order to improve the filtration accuracy and internal cleanliness. The first upstream part refers to the pre-filtration area of ​​the main fluid filter, and the first downstream part refers to the post-filtration area of ​​the main fluid filter. The liquid outlet module is used to collect the filtrate, and it is more necessary to maintain the sealing and sterility of the liquid outlet module to ensure that the sterility of the filtrate meets the use requirements; the first upstream end refers to the pre-filtration area of ​​the main air filter, and the first downstream end refers to the post-filtration area of ​​the main air filter, that is, the filtered sterile test gas is passed into the main fluid filter for integrity testing. Therefore, it is necessary to ensure the sealing and sterility of the first downstream part and the first downstream end; and when performing the integrity test, it is necessary to wet the main fluid filter and the main air filter and pass the test gas, The wetting liquid and the test gas will be discharged from the first downstream part and the first downstream end respectively. There is a risk of backflow contamination during the discharge process. Therefore, the filter component of the present invention is sealed and connected to the first waste container on the liquid outlet module, and a second waste container is arranged at the first downstream end of the main air filter. The interiors of the first waste container and the second waste container are both isolated from the outside world, thereby improving the internal sealing of the filter component; the first waste container and the second waste container can respectively receive the wetting liquid and the test gas, avoiding the wetting liquid and the test gas from being directly discharged into the environment, and can ensure the sealing of the entire flow path and the sterility requirements of the use environment. At the same time, the wetting liquid and the test gas flow into the corresponding containers in the waste discharge module. The waste discharge module can be a device with or subsequently set with an end point indication function to realize the end point indication of the wetting and integrity tester.

[0014] Preferably, the waste discharge module further comprises a third waste discharge container sealedly connected to the first upstream portion of the main fluid filter, and the third waste discharge container is at least used to receive waste gas discharged when the main fluid filter is wetted.

[0015] The main fluid filter is large in size and contains a lot of air, which has a great impact on the main fluid filter. Therefore, during the wetting process, the internal space of the main fluid filter will gradually be filled with wetting liquid and the waste gas will be discharged from the first upstream part. The third waste container is sealed with the first upstream part and can receive the waste gas and overflowed wetting liquid discharged when wetting the main fluid filter, which plays a prompting role and is conducive to completely removing the air in the main fluid filter and optimizing the filtering effect. The third waste container can also seal the first upstream part. Although the first upstream part is the pre-filtration area of ​​the main fluid filter and does not contact the filtrate, in some processes with higher sterility requirements, sealing the first upstream part can improve the overall sealing and sterility of the main fluid filter to meet the sterility requirements of the filtrate.

[0016] Preferably, the first waste discharge container, the second waste discharge container and the third waste discharge container are containers with an initial internal air pressure of zero and observable contents, so as to ensure that the wetting liquid and the test gas will not be subjected to reverse pressure and cause backflow when discharged, thereby ensuring the smooth flow of the wetting liquid and the test gas. In particular, the flow of the test gas has an impact on the results of the integrity test. Such a setting can improve the accuracy and test efficiency of the integrity test; the observable contents make the prompts of the waste discharge module more intuitive and faster.

[0017] Preferably, the first waste discharge container, the second waste discharge container and the third waste discharge container are all transparent bags. The initial state of the transparent bags is that there is no air inside to ensure that there is no negative pressure inside the container, and the instructions are clear, so that the various steps of the filtration assembly are easier to connect and operate, which is conducive to improving work efficiency.

[0018] Preferably, the filter assembly further comprises at least one set of auxiliary fluid filters, the auxiliary fluid filters being located upstream of the primary fluid filter and being sealed in series in a fluid flow order, the auxiliary fluid filters comprising a second upstream portion and a second downstream portion, the second downstream portion being sealedly connected to the first upstream portion or the second upstream portion of another auxiliary fluid filter; the waste discharge module further comprising a fourth waste discharge container being sealedly connected to the second upstream portion, the fourth waste discharge container being at least used to receive waste gas discharged when wetting the auxiliary fluid filters;

[0019] The second upstream portion is sealedly connected to the first downstream end, the liquid inlet module is sealedly connected to the second upstream portion and can communicate with the auxiliary fluid filter; the second upstream portion has an interface for sealing connection to a filter integrity testing device, so that the test gas passing through the filter integrity testing device can pass only through the auxiliary fluid filter, or pass through the main air filter and the auxiliary fluid filter in sequence; or, it further includes a secondary air filter corresponding to the secondary fluid filter one by one, the secondary air filter includes a second upstream end and a second downstream end, the second upstream portion is sealedly connected to the second downstream end, the waste module also includes a fifth waste container sealedly connected to the second downstream end, the liquid inlet module is sealedly connected to both the second upstream portion and the second upstream end, and can communicate with the auxiliary fluid filter or the auxiliary air filter, the second upstream portion and / or the second upstream end has an interface that can be sealedly connected to a filter integrity testing device, so as to allow the test gas passing through the filter integrity testing device to pass only through the secondary fluid filter, or pass through the secondary air filter and the secondary fluid filter in sequence, or pass through the secondary air filter only.

[0020] The function of the auxiliary fluid filter is to pre-filter the feed liquid, and it can cooperate with the main fluid filter to achieve multiple filtrations to improve the filtration accuracy and filtrate purity; therefore, the auxiliary fluid filter is located upstream of the main fluid filter, and the number can be set to one or more as needed; the auxiliary fluid filter also needs to undergo an integrity test, and the filtered test gas also needs to pass through the auxiliary fluid filter after wetting. The auxiliary fluid filter can use the main air filter to filter the test gas, or a corresponding auxiliary air filter can be set to filter the test gas; therefore, the auxiliary fluid filter and the auxiliary air filter need to be wetting and the test gas needs to be passed through. Since the downstream of the auxiliary fluid filter is another auxiliary The fluid filter or primary fluid filter therefore does not require a separate, sealed waste container and can share the same waste container (the first waste container) as the primary fluid filter. The fourth waste container functions similarly to the third waste container. Because the fluid filter contains a significant amount of air, this excess air significantly impacts the auxiliary fluid filter. During the wetting process, the auxiliary fluid filter's internal space gradually fills with wetting liquid, forcing waste gas out of the second upstream portion. The fourth waste container, sealed to the second upstream portion, receives waste gas and overflowing wetting liquid during wetting, acting as a reminder, facilitating the complete removal of air from the auxiliary fluid filter and optimizing filtration efficiency. The fifth waste container, sealed to the second downstream end of the auxiliary air filter, serves the same purpose as the second waste container: ensuring the sterility of the test gas after filtration by the auxiliary air filter and preventing contamination by backflow of wetting liquid. Both the fourth and fifth waste containers are isolated from the outside world, improving the internal seal and sterility of the filter assembly. They also serve as a reminder when wetting liquid and test gas flow into the corresponding waste module, guiding the next step.

[0021] Preferably, a top wash bag for receiving top wash liquid is provided between the first downstream portion and the liquid outlet module; the interface of the first upstream end is also used to be sealedly connected to a container integrity testing device to allow test gas to pass into the top wash bag.

[0022] The function of the top wash bag is to receive the feed liquid of the filter component during the top wash process. When the cost of the feed liquid is high, the wetting liquid and the feed liquid can be of different materials. In this case, before the filtration step, the wetting liquid needs to be discharged first, that is, the wetting liquid in the flow path of the fluid filter component is top washed with the feed liquid. In the process of discharging the wetting liquid, the main fluid filter may also be connected to the outside world and contaminated. The top wash bag can also serve to isolate and seal the main fluid filter from the external environment during the top wash process before filtration. The integrity of the top wash bag needs to be confirmed by a container integrity test device and test gas to ensure the sealing and sterility of the first downstream part of the main fluid filter.

[0023] Preferably, the filtration assembly further comprises a micro-limit sampling bag, which is hermetically connected to the first upstream portion. The micro-limit sampling bag is used to sample the liquid that has not entered the fluid filter, so as to sample and measure the properties of the liquid, and thus set the process parameters of subsequent filtration based on the test results. When only the main fluid filter in the filtration assembly is used to filter the liquid, the micro-limit sampling bag is hermetically connected to the first upstream portion to ensure that the unfiltered liquid is collected.

[0024] Preferably, the filtration assembly further comprises a micro-limit sampling bag, which is sealed and connected to the second upstream portion of the first auxiliary fluid filter located in the fluid flow sequence. The function of the micro-limit sampling bag is to sample the feed liquid that has not entered the fluid filter, so as to sample and measure the properties of the feed liquid, and thus set the process parameters of the subsequent filtration according to the test results; generally speaking, the micro-limit sampling bag is set upstream of the first fluid filter in the feed liquid flow direction to ensure that the unfiltered feed liquid is collected. When the fluid filtration assembly includes one or more auxiliary fluid filters, the micro-limit sampling bag is sealed and connected to the second upstream portion of the first auxiliary fluid filter located in the fluid flow sequence.

[0025] Preferably, the liquid inlet module includes a first liquid inlet pump and a first liquid inlet flow path, the first liquid inlet flow path has a liquid inlet port connected to a wetting liquid source or a feed liquid source, the first liquid inlet pump is provided on the first liquid inlet flow path to control the flow of fluid in the first liquid inlet flow path, and the first liquid inlet flow path is sealedly connected to the first upstream portion;

[0026] The liquid inlet module also includes a second liquid inlet pump and a second liquid inlet flow path, the second liquid inlet flow path has a liquid inlet port connected to the wetting liquid source, the second liquid inlet pump is arranged on the second liquid inlet flow path to control the fluid flow in the second liquid inlet flow path, and the second liquid inlet flow path can be sealed and connected to the first upstream end.

[0027] Separating the liquid inlet flow paths of the main fluid filter and the main air filter can reduce pipeline switching in the liquid inlet module. The first liquid inlet pump and the first liquid inlet flow path corresponding to the main fluid filter can be used to transport wetting liquid and feed liquid, and the second liquid inlet pump and the second liquid inlet flow path corresponding to the main air filter are only used to transport wetting liquid, which is simpler to operate and more efficient.

[0028] Preferably, the liquid inlet module includes a first liquid inlet pump and a first liquid inlet flow path, the first liquid inlet flow path has a liquid inlet port connected to a wetting liquid source or a feed liquid source, the first liquid inlet pump is provided on the first liquid inlet flow path to control the flow of fluid in the first liquid inlet flow path, and the first liquid inlet flow path is sealedly connected to the second upstream portion of the auxiliary fluid filter located first in the fluid flow sequence;

[0029] The liquid inlet module further includes a second liquid inlet pump and a second liquid inlet flow path, wherein the second liquid inlet flow path has a liquid inlet port connected to a wetting liquid source, and the second liquid inlet pump is disposed on the second liquid inlet flow path to control the flow of fluid in the second liquid inlet flow path, and the second liquid inlet flow path can be sealed and connected to the first upstream end.

[0030] When the auxiliary fluid filter has a one-to-one correspondence with an auxiliary air filter, the second liquid inlet flow path can be sealed and communicated with the second upstream end.

[0031] Separating the liquid inlet flow paths of the fluid filter and the air filter can reduce the pipeline switching in the liquid inlet module. The first liquid inlet pump and the first liquid inlet flow path corresponding to the main fluid filter and the auxiliary fluid filter can be used to transport the wetting liquid and the feed liquid, and the second liquid inlet pump and the second liquid inlet flow path corresponding to the main air filter and the auxiliary air filter are only used to transport the wetting liquid, which makes the operation simpler and more efficient.

[0032] Preferably, a first pressure sensor is provided on the first liquid inlet flow path and is communicatively connected to the control module. The first pressure sensor is capable of detecting the fluid pressure in the first liquid inlet flow path. After the detection information is fed back to the control module, the fluid velocity and pressure of the first liquid inlet pump, the wetting liquid source, or the feed liquid source can be adjusted to protect various components in the filter assembly.

[0033] Preferably, the liquid outlet module includes a liquid outlet flow path connected to the first downstream portion, and a second pressure sensor is provided on the liquid outlet flow path; the first pressure sensor and the second pressure sensor can both be communicatively connected to the control module.

[0034] When only the main fluid filter is used to filter the feed liquid, the first pressure sensor and the second pressure sensor are respectively located upstream and downstream of the main fluid filter. Therefore, by comparing the numerical difference between the first pressure sensor and the second pressure sensor, the feed liquid pressure differential experienced by the main fluid filter can be known. If the feed liquid pressure differential is too large, it means that the main fluid filter is clogged and the entire component needs to be replaced in time; or, by controlling the feed liquid inlet amount and flow rate in the first liquid inlet flow path, the feed liquid pressure differential is controlled within a reasonable range to protect the main fluid filter; when the filter assembly filters the feed liquid through the auxiliary fluid filter and the main fluid filter, the first pressure sensor and the second pressure sensor are respectively located upstream of the auxiliary fluid filter and downstream of the main fluid filter; therefore, by comparing the numerical difference between the first pressure sensor and the second pressure sensor, the feed liquid pressure differential experienced by the main fluid filter and the auxiliary fluid filter can be known, thereby controlling the feed liquid inlet amount and flow rate in the first liquid inlet flow path, and controlling the feed liquid pressure differential is controlled within a reasonable range to protect the main fluid filter and the auxiliary fluid filter.

[0035] Preferably, a third pressure sensor is provided between the second downstream portion and the first upstream portion, and the third pressure sensor is communicatively connected to the control module. By comparing the readings of the third pressure sensor with those of the first pressure sensor, the fluid pressure differential acting on the auxiliary fluid filter can be determined. By comparing the readings of the second pressure sensor with those of the third pressure sensor, the fluid pressure differential acting on the primary fluid filter can be determined. This ensures that differential pressure testing can be performed on each fluid filter, resulting in higher accuracy and easier identification of a faulty fluid filter.

[0036] Preferably, the liquid inlet includes a wetting liquid inlet and a feed liquid inlet that are independent of each other; when the liquid inlet module includes only one liquid inlet flow path, the liquid inlet flow path includes a wetting liquid inlet and a feed liquid inlet that are independent of each other, and also includes interfaces connected to the fluid filter and the air filter respectively; when the liquid inlet module includes a first liquid inlet flow path and a second liquid inlet flow path, the first liquid inlet flow path is used to transport the wetting liquid and the feed liquid to the fluid filter, and therefore has a wetting liquid inlet and a feed liquid inlet that are independent of each other, and the second liquid inlet flow path is used to transport the wetting liquid to the air filter, and therefore has an independent wetting liquid inlet.

[0037] Preferably, the liquid outlet module includes independent product and waste outlets, the waste outlets being sealedly connected to the first waste container. The product outlet is connected to a filtrate storage device to collect filtrate during the filtration process. The first waste container is used to collect waste liquid from various stages of the fluid filtration assembly, including but not limited to wetting fluid, residual feed liquid from the previous filtration, or a mixture of wetting fluid and feed liquid. Separating the two facilitates operation while ensuring the purity of the filtrate.

[0038] In order to achieve the above object, the present invention also adopts the following technical solutions:

[0039] A filtration system comprising the above-mentioned filtration assembly, further comprising a filter integrity testing device and a container integrity testing device;

[0040] The filter integrity testing device can be connected to a test gas source to perform integrity testing on the primary fluid filter or the primary air filter or the secondary fluid filter or the secondary air filter;

[0041] The container integrity testing device can be connected to a test air source to perform an integrity test on the top wash bag or the first waste container and detect the sealing of the flow path from the main air filter to the top wash bag or the first waste container.

[0042] The filtration system of the present invention utilizes a filter integrity testing device to perform an integrity test on the main fluid filter or the main air filter or the auxiliary fluid filter or the auxiliary air filter, and utilizes a container integrity testing device to perform an integrity test on the top wash bag or the first waste container and detect the sealing of the flow path from the main air filter to the top wash bag or the first waste container. During this process, the waste gas and wetting liquid discharged from the main fluid filter or the auxiliary fluid filter are input into the corresponding waste container, and the wetting liquid discharged from the main air filter or the auxiliary air filter is input into the corresponding waste container, so as to avoid backflow contamination of each filter during testing, and also to avoid the wetting liquid, waste gas and test gas being directly discharged into the external environment, thereby ensuring the sterility of the entire filtration system and the external environment.

[0043] Preferably, the filtration system also includes a control module to control the execution of the filter integrity test program or the filtration program or the container integrity test program. The purpose of the control module is to improve the degree of automation of the entire fluid filtration system. Through parameter setting, precise control of each component in the fluid filtration system can be achieved, which can not only protect each fluid filter, but also realize rapid switching of each flow path, thereby improving operational efficiency and saving expensive feed liquid.

[0044] Preferably, the filtration system also includes a weight sensing device arranged on the top wash bag, and the weight sensing device is communicatively connected to the control module to transmit the amount of slurry in the top wash bag to the control module. The control module is also used to execute the top wash procedure based on the amount of slurry.

[0045] When the weight sensing device detects that the weight of the top wash bag reaches the set value, it means that the flow path in the entire fluid filtration assembly has been completely wetted by the liquid and the next step of filtration can be carried out. The weight sensing device can send a signal to the control module to notify the staff to proceed to the next operation, or the control module can automatically perform the next operation, thereby improving the degree of automation of the fluid filtration assembly and reducing the waste of expensive liquid.

[0046] In order to achieve the above object, the present invention also adopts the following technical solutions:

[0047] An online integrity testing method, using the above-mentioned filtration system, comprises the following steps:

[0048] 1. Container integrity test steps:

[0049] Maintaining sealed communication between the container integrity testing device and the first upstream end, connecting the main air filter to the main fluid filter and then to the first waste container, and closing the communication between the first upstream portion, the first downstream portion and other components, allowing the test gas to sequentially pass through the container integrity testing device and flow to the main air filter, the main fluid filter and then to the first waste container, thereby performing an integrity test on the first waste container;

[0050] 2. Main fluid filter integrity test steps:

[0051] Wetting the main fluid filter and keeping the filter integrity testing device connected to the main air filter and the main fluid filter to perform an integrity test on the main fluid filter;

[0052] 3. Main air filter integrity test steps:

[0053] Wetting the main air filter until the wetting liquid appears in the second waste container, and then maintaining the filter integrity testing device connected to the main air filter to perform an integrity test on the main air filter;

[0054] 4. Filtration steps:

[0055] Keeping the liquid inlet module connected to the main fluid filter, the filtrate passes through the main fluid filter to the liquid outlet module to be filtered, and the filtrate is collected in the liquid outlet module;

[0056] 5. Steps for retesting the integrity of the main fluid filter:

[0057] The filter integrity testing device is kept in direct connection with the main fluid filter to perform an integrity test on the main fluid filter.

[0058] The online integrity testing method of the present invention first performs a container integrity test on the filtration system to determine the sealing and integrity of the bag body, thereby avoiding contamination of the filtration system due to damage to the bag body; then performs integrity tests on the main fluid filter and the main air filter to ensure the sealing and sterility of each component before filtering the feed liquid, thereby meeting the sterility requirements of the filtrate, avoiding expensive waste of filtrate, and improving production efficiency; finally, a review of the integrity of the main fluid filter is performed to verify the integrity of the entire filtration system during the filtration process to prove the sterility of the filtrate; in this process, the waste gas and wetting liquid discharged from the main fluid filter or the auxiliary fluid filter are input into the corresponding waste discharge container, and the wetting liquid discharged from the main air filter or the auxiliary air filter is input into the corresponding waste discharge container, thereby avoiding backflow contamination of each filter during testing, and also avoiding the wetting liquid, waste gas and test gas being directly discharged into the external environment, thereby ensuring the sterility of the entire filtration system and the external environment.

[0059] Preferably, when the filtration system includes a top wash bag, the method further comprises a top wash bag integrity test step:

[0060] Keep the container integrity testing device sealedly connected to the first upstream end, connect the main air filter to the main fluid filter to the top wash bag, and close the connection between the first upstream part, the first downstream part and other components. The test gas passes through the container integrity testing device in sequence and flows to the main air filter, the main fluid filter and the top wash bag to perform an integrity test on the top wash bag.

[0061] Preferably, when the filtration system includes a third waste container, the main fluid filter integrity testing step includes:

[0062] disconnecting the main fluid filter from the liquid outlet module, connecting the liquid inlet module to the first upstream portion of the main fluid filter and supplying a wetting liquid to the main fluid filter until the wetting liquid appears in the third waste container, and then stopping the liquid inlet module;

[0063] After the first preset time, the main fluid filter is connected to the liquid outlet module, the liquid inlet module is started and the main fluid filter is dynamically flushed until the second preset time is reached, the wetting liquid is discharged into the first waste container to achieve complete wetting of the main fluid filter, and then the main fluid filter is subjected to an integrity test.

[0064] Preferably, when the filtration system includes a secondary fluid filter, and a fourth waste container is connected to the second upstream portion of the secondary fluid filter, the method further comprises a secondary fluid filter integrity testing step: wetting the secondary fluid filter until wetting liquid appears in the fourth waste container, and maintaining the filter integrity testing device connected to the secondary fluid filter via the main air filter or the secondary air filter to perform an integrity test on the secondary fluid filter; and / or

[0065] When the filtration system includes a secondary air filter, and the second downstream end of the secondary air filter is sealedly connected to a fifth waste container, the method further includes a secondary air filter integrity testing step: wetting the secondary air filter until a wetting liquid appears in the fifth waste container, and then maintaining the filter integrity testing device connected to the secondary air filter to perform an integrity test on the secondary air filter; and / or

[0066] When a micro-limit sampling bag is connected to the upstream part of the first main fluid filter or auxiliary fluid filter located in the fluid flow sequence, the filtration step also includes: controlling the liquid inlet module to be connected to the first main fluid filter or auxiliary fluid filter located in the fluid flow sequence, and starting the liquid inlet module until the liquid entering the micro-limit sampling bag reaches a preset value, and then stopping the liquid inlet module.

[0067] In summary, compared with the prior art, the present invention has at least the following beneficial effects:

[0068] The filter assembly of the present invention is sealedly connected to the first waste container on the liquid outlet module, and a second waste container is arranged at the first downstream end of the main air filter. The interiors of the first waste container and the second waste container are both isolated from the outside world, thereby improving the internal sealing of the filter assembly; the first waste container and the second waste container can respectively receive the wetting liquid and the test gas, thereby avoiding the wetting liquid and the test gas from being directly discharged into the environment, thereby ensuring the sealing of the entire flow path and the sterility requirements of the use environment, while the wetting liquid and the test gas flow into the corresponding waste discharge module, and also realizing the end point indication of the wetting and integrity tester.

[0069] The filtration system and online integrity testing method of the present invention utilize a filter integrity testing device to perform an integrity test on the main fluid filter or the main air filter or the auxiliary fluid filter or the auxiliary air filter, utilize a container integrity testing device to perform an integrity test on the top wash bag or the first waste container and detect the sealing of the flow path from the main air filter to the top wash bag or the first waste container. During this process, the waste gas and wetting liquid discharged from the main fluid filter or the auxiliary fluid filter are input into the corresponding waste container, and the wetting liquid discharged from the main air filter or the auxiliary air filter is input into the corresponding waste container, to avoid backflow contamination of each filter during testing, and to avoid the wetting liquid, waste gas and test gas being directly discharged into the external environment, thereby ensuring the sterility of the entire filtration system and the external environment. BRIEF DESCRIPTION OF THE DRAWINGS

[0070] In order to more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the specific embodiments or the description of the prior art. Obviously, the drawings described below are some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative work.

[0071] Figure 1 This is a schematic diagram of the framework of the filter assembly according to the first embodiment of the present invention.

[0072] Figure 2 Schematic diagram of the framework of the filtering system based on the filtering component of the first embodiment of the present invention.

[0073] Figure 3 This is a schematic diagram of the framework of the filtering system according to the second embodiment of the present invention.

[0074] Figure 4 This is a schematic diagram of the framework of the filtration system according to the second embodiment of the present invention, specifically a schematic diagram of the framework when the wetting and integrity tests are performed on the main fluid filter and the auxiliary fluid filter.

[0075] Figure 5 This is a schematic diagram of the framework of the filtration system according to the second embodiment of the present invention, specifically a schematic diagram of the framework during the wetting and integrity testing of the main air filter and the auxiliary air filter, as well as the filtration steps.

[0076] Figure 6 This is a schematic diagram of the framework of the filtration system according to the second embodiment of the present invention, specifically a schematic diagram of the framework when the integrity of the main fluid filter and the auxiliary fluid filter are reviewed.

[0077] Description of Reference Numerals

[0078] 10. Main fluid filter; 11. First upstream portion; 12. First downstream portion; 13. First valve; 14. Third waste container; 15. Micro-limit sampling bag; 16. Top wash bag; 161. Weight sensor; 17. Four-way port; 171. Third valve; 172. Fourth valve; 173. Fifth valve; 18. Opening and closing element;

[0079] 20. Main air filter; 21. First upstream end; 22. First downstream end; 23. Second waste container; 24. Sixth valve;

[0080] 30. Liquid inlet module; 31. First liquid inlet pump; 32. First liquid inlet flow path; 321. Wetting liquid inlet; 322. Feed liquid inlet; 323. Second valve; 33. Second liquid inlet pump; 34. Second liquid inlet flow path;

[0081] 40. Liquid outlet module; 41. Product outlet; 42. First row of waste containers;

[0082] 50. Auxiliary fluid filter; 51. Second upstream portion; 52. Second downstream portion; 53. Seventh valve; 54. Eighth valve; 55. Fourth waste container;

[0083] 60. Auxiliary air filter; 61. Second upstream end; 62. Second downstream end; 63. Ninth valve; 64. Fifth waste container;

[0084] 70. Filter integrity test device; 71. First on-off valve; 72. Three-way solenoid valve;

[0085] 80. Container integrity testing device; 81. Second on-off valve;

[0086] 90. First pressure sensor; 91. Second pressure sensor; 92. Third pressure sensor. DETAILED DESCRIPTION

[0087] The technical solution of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the embodiments described are only some embodiments of the present invention, not all embodiments. All other embodiments obtained by ordinary technicians in this field based on the embodiments of the present invention without making any creative efforts shall fall within the scope of protection of the present invention.

[0088] In the description of the present invention, it should be noted that the terms "center," "upper," "lower," "left," "right," "vertical," "horizontal," "inner," and "outer," etc., indicating orientations or positional relationships, are based on the orientations or positional relationships shown in the accompanying drawings and are intended solely to facilitate and simplify the description of the present invention. They are not intended to indicate or imply that the devices or components referred to must have, be constructed, or operate in a specific orientation, and therefore should not be construed as limitations on the present invention. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and should not be construed as indicating or implying relative importance.

[0089] In the description of the present invention, it should be noted that, unless otherwise expressly specified or limited, the terms "mounted," "connected," and "connected" should be understood in a broad sense. For example, they may refer to fixed, detachable, or integral connections; mechanical or electrical connections; direct or indirect connections through an intermediate medium; and internal communication between two components. Those skilled in the art will understand the specific meanings of the above terms in the present invention based on the specific circumstances.

[0090] like Figure 1As shown, the filter assembly of the embodiment of the present invention includes a liquid inlet module 30, a liquid outlet module 40, a main fluid filter 10 and a main air filter 20 located upstream of the main fluid filter 10; the main fluid filter 10 includes a first upstream portion 11 and a first downstream portion 12, the first downstream portion 12 is sealedly connected to the liquid outlet module 40, and the main air filter 20 includes a first upstream end 21 and a first downstream end 22; it also includes a waste discharge module, the waste discharge module includes a first waste discharge container 42 sealedly connected to the liquid outlet module 40, and a second waste discharge container 23 sealedly connected to the first downstream end 22 of the main air filter 20; the liquid inlet module 30 is connected to the first upstream portion 11 and the first downstream portion 12 The upstream ends 21 are sealed and connected, and can communicate with the main fluid filter 10 or the main air filter 20. The liquid inlet module 30 has a liquid inlet for connecting to a wetting liquid source or a feed liquid source. The first upstream end 21 and / or the first upstream portion 11 have an interface that can be sealed and communicated with the filter integrity testing device 70 or the container integrity testing device, so as to allow the test gas passing through the filter integrity testing device or the container integrity testing device to pass only through the main air filter 20, or only through the main fluid filter 10 and then pass into the first waste container 42, or pass through the main air filter 20 and the main fluid filter 10 in sequence and then pass into the first waste container 42.

[0091] The main fluid filter 10 plays the main filtering role in the entire filter assembly and is used to produce filtrate; the first upstream part 11 refers to the pre-filtration area of ​​the main fluid filter 10, the first downstream part 12 refers to the post-filtration area of ​​the main fluid filter 10, and the liquid outlet module 40 is used to collect the filtrate; in order to ensure the sterility of the filtrate, the main fluid filter 10 needs to ensure its integrity, and the sealing and sterility of the liquid outlet module 40 must also be maintained.

[0092] In order to ensure the integrity of the main fluid filter 10, an integrity test is required. The integrity test method is to fully wet the main fluid filter 10, pass the test gas into the main fluid filter 10, and use the filter integrity testing device 70 to test it. In this process, the sterility of the test gas also needs to be maintained. Therefore, a main air filter 20 needs to be set to filter the test gas. The first upstream end 21 refers to the pre-filtration area of ​​the main air filter 20, and the first downstream end 22 refers to the post-filtration area of ​​the main air filter 20. That is, the filtered sterile test gas is passed into the main fluid filter 10 for integrity testing. Therefore, it is necessary to ensure the sealing and sterility of the first downstream part 12 and the first downstream end 22; at the same time, it is also necessary to perform an integrity test on the main air filter 20 to ensure the sterility of the test gas and avoid contamination caused by damage to the main air filter 20. The contaminated test gas passing into the main fluid filter 10 and the pipeline in the fluid filtration assembly will also cause contamination, making it difficult to ensure the sterility of the filtrate. Therefore, it is also necessary to perform an integrity test on the main air filter 20.

[0093] In the content disclosed in the present invention, the upstream part refers to the area that has not passed through the fluid filter, that is, in front of the filter membrane; the downstream part refers to the area that has passed through the fluid filter, that is, after the filter membrane; the upstream end refers to the area that has not passed through the air filter, that is, in front of the filter membrane; the downstream end refers to the area that has passed through the air filter, that is, after the filter membrane.

[0094] When conducting an integrity test, the main fluid filter 10 and the main air filter 20 need to be moistened and test gas needs to be introduced. The moistening liquid and the test gas will be discharged from the first downstream portion 12 and the first downstream end 22 respectively. There is a risk of backflow contamination during the discharge process. Therefore, the filter assembly of the present invention is sealed and connected to a first waste container 42 on the liquid outlet module 40, and a second waste container 23 is provided at the first downstream end 22 of the main air filter 20. The interiors of the first waste container 42 and the second waste container 23 are both isolated from the outside world, thereby improving the internal sealing of the filter assembly; the first waste container 42 and the second waste container 23 can respectively receive the moistening liquid and the test gas, avoiding the direct discharge of the moistening liquid and the test gas into the environment, thereby ensuring the sealing of the entire flow path and the sterility requirements of the use environment. At the same time, the moistening liquid and the test gas flow into the corresponding waste discharge module. The waste discharge module can be a device having or subsequently provided with an endpoint indication function to achieve the endpoint indication of the wetting and integrity tester.

[0095] After confirming the integrity of the main fluid filter 10 and the main air filter 20, the liquid inlet module 30 can also be directly connected to the main fluid filter 10, so that the feed liquid is filtered through the main fluid filter 10. At this time, the first waste container 42 is also used to receive the liquid flowing out of the first downstream part 12 of the main fluid filter 10, including the wetting liquid, the filtrate and the mixed liquid. It should be noted that the wetting liquid and the mixed liquid are placed separately from the filtrate to avoid affecting the purity of the collected filtrate.

[0096] The main fluid filter 10 has a large volume and a lot of air inside it, which has a great impact on the main fluid filter 10. During the wetting process, the internal space of the main fluid filter 10 will gradually be filled with the wetting liquid and the exhaust gas will be discharged from the first upstream part 11. Figure 1As shown, the waste discharge module also includes a third waste discharge container 14 sealed with the first upstream portion 11 of the main fluid filter 10. The third waste discharge container 14 is at least used to receive the waste gas discharged and the overflowed wetting liquid when the main fluid filter 10 is wetting, and serves as a prompt, which is conducive to confirming that the air in the main fluid filter 10 is completely removed and the filtering effect is optimized; and the third waste discharge container 14 can also seal the first upstream portion 11. Although the first upstream portion 11 is the pre-filtration area of ​​the main fluid filter 10 and does not contact the filtrate, in some processes with higher sterility requirements, sealing the first upstream portion 11 can improve the overall sealing and sterility of the main fluid filter 10 to meet the sterility requirements of the filtrate.

[0097] The first waste container 42, the second waste container 23 and the third waste container 14 are all containers with zero initial internal pressure and observable contents, so as to ensure that the wetting liquid and test gas will not be subjected to reverse pressure and cause backflow when discharged, thus ensuring the smooth flow of the wetting liquid and test gas. In particular, the flow of the test gas has an impact on the results of the integrity test. Such a setting can improve the accuracy and efficiency of the integrity test; the observable contents make the prompts of the waste discharge module more intuitive and faster. Figure 1 In the first embodiment shown, the first waste container 42, the second waste container 23, and the third waste container 14 are all transparent bags. The initial state of the transparent bags is that they are airtight inside to ensure that there is no negative pressure inside the containers. The instructions are clear, making it easier to connect and operate the various steps of the filtration assembly, which is conducive to improving work efficiency.

[0098] like Figure 1 As shown, the first upstream portion 11 is also sealed with a micro-sampling bag 15. This bag is used to sample the liquid before it enters the fluid filter, measure its properties, and set subsequent filtration process parameters based on the test results. The pipelines connecting the third waste container 14 and the micro-sampling bag 15 to the first upstream portion 11 are each equipped with an opening and closing element 18 to control the flow of fluid between the first upstream portion 11, the third waste container 14, and the micro-sampling bag 15.

[0099] like Figure 1 As shown, a top wash bag 16 for receiving top wash liquid is disposed between the first downstream portion 12 and the liquid outlet module 40. The top wash bag 16 also serves to isolate and seal the main fluid filter 10 from the external environment during the top wash process prior to filtration. The liquid outlet module 40 includes a product outlet 41 or a first waste container 42, which are sealedly connected to the first downstream portion 12. The product outlet 41 is used to connect to a filtrate storage device to collect filtrate during the filtration process. The first waste container 42 is used to collect waste liquid from various stages of the fluid filtration assembly, including but not limited to the wetting liquid, residual liquid from the previous filtration, or a mixture of the wetting liquid and the liquid.

[0100] like Figure 1 In the illustrated embodiment 1, the filter assembly only has a main fluid filter 10 as a feed liquid filtering device, the main air filter 20 is located upstream of the main fluid filter 10, the liquid inlet module 30 and the liquid outlet module 40 both include pipelines and valves for controlling the on-off of the pipelines, the pipelines of the liquid inlet module 30 are respectively sealed and connected to the upstream of the main air filter 20 and the main fluid filter 10 and are selectively connected, and the pipelines of the liquid outlet module 40 are sealed and connected to the downstream of the main fluid filter 10 and can select the product outlet 41.

[0101] like Figure 1 As shown, a pipeline and a valve for controlling the on / off of the pipeline are provided between the main air filter 20 and the main fluid filter 10, specifically including a first valve 13 provided between the first downstream end 22 and the first upstream portion 11. The first valve 13 can control the on / off of the first upstream portion 11 and the first downstream end 22 while maintaining a sealed connection between the two.

[0102] like Figure 1 As shown, the liquid inlet module 30 includes a first liquid inlet pump 31 and a first liquid inlet flow path 32. The first liquid inlet flow path 32 has a liquid inlet port connected to a wetting liquid source or a feed liquid source. The first liquid inlet pump 31 is arranged on the first liquid inlet flow path 32 to control the flow rate and flow amount of the fluid in the first liquid inlet flow path 32, and the first liquid inlet flow path 32 is sealed with the first upstream portion 11. A second valve 323 is provided on the first liquid inlet flow path 32 for controlling the on and off of the first liquid inlet flow path 32. The first liquid inlet flow path 32 includes a first interface for connecting to the wetting liquid source and a second interface for connecting to the feed liquid source; valves for controlling on and off are respectively provided on the first interface and the second interface, and the first liquid inlet pump 31 is located downstream of the connection point between the first interface and the second interface. The liquid inlet module 30 also includes a second liquid inlet pump 33 and a second liquid inlet flow path 34. The second liquid inlet flow path 34 has a liquid inlet port connected to the wetting liquid source. The second liquid inlet pump 33 is arranged on the second liquid inlet flow path 34 to control the flow speed and flow amount of the fluid in the second liquid inlet flow path 34, and the second liquid inlet flow path 34 can be sealed and connected with the first upstream end 21. A valve for controlling the opening and closing of the second liquid inlet flow path 34 can also be set on the second liquid inlet flow path 34.

[0103] Separating the inlet flow paths for the main fluid filter 10 and the main air filter 20 can reduce piping switching in the inlet module 30. The first inlet pump 31 and first inlet flow path 32 corresponding to the main fluid filter 10 can be used to transport the wetting liquid and the feed liquid, while the second inlet pump 33 and second inlet flow path 34 corresponding to the main air filter 20 are only used to transport the wetting liquid, making operation simpler and more efficient. The first inlet pump 31 and the second inlet pump 33 can be peristaltic pumps.

[0104] Of course, in other embodiments, the liquid inlet flow path of the liquid inlet module 30 can be connected to the first upstream part 11 and the first upstream end 21 respectively, and the flow direction of the wetting liquid therein can be controlled by the valve on the liquid inlet flow path, thereby realizing the wetting of the main fluid filter 10 and the main air filter 20 in sequence.

[0105] like Figure 1 As shown, a four-way interface 17 is connected between the liquid outlet module 40 and the first downstream portion 12, which is respectively connected to the first downstream portion 12, the top wash bag 16, the first waste container 42 and the product outlet 41. A third valve 171 is provided between the top wash bag 16 and the four-way interface 17, a fourth valve 172 is provided between the product outlet 41 and the four-way interface 17, a fifth valve 173 is provided between the first waste container 42 and the four-way interface 17; and a sixth valve 24 is provided between the second waste container 23 and the first downstream end 22.

[0106] In this embodiment, the first valve 13 , the second valve 323 , the third valve 171 , the fourth valve 172 , the fifth valve 173 and the sixth valve 24 may be pinch valves to ensure the sealing inside the pipeline while controlling the on-off of the pipeline.

[0107] A first pressure sensor 90 is provided on the first liquid inlet flow path 32, and the first pressure sensor 90 can be communicated with the control module, and the first pressure sensor 90 can detect the fluid pressure on the first liquid inlet flow path 32; the liquid outlet module 40 includes a liquid outlet flow path connected to the first downstream part 12, and a second pressure sensor 91 is provided on the liquid outlet flow path; the first pressure sensor 90 and the second pressure sensor 91 can both be communicated with the control module; when only the main fluid filter 10 is used to filter the feed liquid, the first pressure sensor 90 and the second pressure sensor 91 are respectively located upstream and downstream of the main fluid filter 10, thereby, by comparing the numerical difference between the first pressure sensor 90 and the second pressure sensor 91, the feed liquid pressure difference applied to the main fluid filter 10 can be known. If the feed liquid pressure difference is too large, it means that the main fluid filter 10 is blocked and the entire component needs to be replaced in time; alternatively, the feed liquid inlet amount and flow rate in the first liquid inlet flow path 32 can be controlled by using the numerical difference to control the feed liquid pressure difference within a reasonable range to protect the main fluid filter 10.

[0108] The liquid inlet includes a wetting liquid inlet 321 and a feed liquid inlet 322 that are independent of each other; when the liquid inlet module 30 includes only one liquid inlet flow path, the liquid inlet flow path includes a wetting liquid inlet 321 and a feed liquid inlet 322 that are independent of each other, and also includes interfaces connected to the fluid filter and the air filter respectively; when the liquid inlet module 30 includes a first liquid inlet flow path 32 and a second liquid inlet flow path 34, the first liquid inlet flow path 32 is used to transport wetting liquid and feed liquid to the fluid filter, and therefore has a wetting liquid inlet 321 and a feed liquid inlet 322 that are independent of each other, and the second liquid inlet flow path 34 is used to transport wetting liquid to the air filter, and therefore has an independent wetting liquid inlet 321.

[0109] Preferably, the liquid outlet module 40 includes a mutually independent product outlet 41 and waste outlet, which are sealedly connected to a first waste container 42. Product outlet 41 is connected to a filtrate storage device to collect filtrate during the filtration process. The first waste container 42 is used to collect waste liquid from various stages of the fluid filtration assembly, including but not limited to the wetting fluid, residual feed liquid from the previous filtration, or a mixture of the wetting fluid and feed liquid. Separating the two facilitates operation while ensuring the purity of the filtrate.

[0110] The filtration system based on the filtration assembly of this embodiment, such as Figure 2 As shown, it also includes a filter integrity testing device 70 and a container integrity testing device 80; the filter integrity testing device 70 can be connected to a test gas source to perform an integrity test on the main fluid filter 10 or the main air filter 20 or the auxiliary fluid filter 50 or the auxiliary air filter 60; the container integrity testing device 80 can be connected to a test gas source to perform an integrity test on the top wash bag 16 or the first waste container 42 and detect the sealing of the flow path from the main air filter 20 to the top wash bag 16 or the first waste container 42.

[0111] The test line of the filter integrity testing device 70 is provided with a first on-off valve 71. The test line can be connected to the main fluid filter 10 or the main air filter 20 and its opening and closing are controlled by the first on-off valve 71. The first on-off valve 71 can be a bidirectional normally closed valve. The test line of the container integrity testing device 80 is provided with a second on-off valve 81. The test line can be connected to the main fluid filter 10 or the main air filter 20 and its opening and closing are controlled by the second on-off valve 81. The second on-off valve 81 can be a bidirectional normally closed valve.

[0112] Preferably, the filtration system also includes a control module to control the execution of the filter integrity test program or the filtration program or the container integrity test program. The purpose of the control module is to improve the degree of automation of the entire fluid filtration system. Through parameter setting, precise control of each component in the fluid filtration system can be achieved, which can not only protect each fluid filter, but also realize rapid switching of each flow path, thereby improving operational efficiency and saving expensive feed liquid.

[0113] Preferably, the filtration system also includes a weight sensor 161 mounted on the top-wash bag 16. This weight sensor 161 is in communication with the control module to transmit information about the amount of liquid in the top-wash bag 16 to the control module. The control module is also configured to execute the top-wash process based on this amount of liquid. Once the weight sensor 161 detects that the weight of the top-wash bag 16 has reached a set value, indicating that the flow path in the entire fluid filtration assembly has been completely wetted with liquid and ready for the next filtration step, the weight sensor 161 can send a signal to the control module to notify a staff member to proceed with the next step, or the control module can automatically execute the next step, thereby improving the automation level of the fluid filtration assembly and reducing the waste of expensive liquid.

[0114] For the filtration system of the above embodiment, the online integrity test method is as follows:

[0115] The various components of the fluid filtration system are connected aseptically, and the filtrate storage bag is connected aseptically at the product outlet 41 .

[0116] 1. Container integrity test steps:

[0117] 1.1. First Waste Discharge Container 42 Integrity Test Step: Maintain sealed communication between the container integrity test device and the first upstream end 21, connect the main air filter 20 to the main fluid filter 10 and then to the first waste discharge container 42, and close the communication between the first upstream portion 11 and the first downstream portion 12 and other components. Allow test gas to sequentially pass through the container integrity test device and flow to the main air filter 20, the main fluid filter 10, and then to the first waste discharge container 42, thereby performing an integrity test on the first waste discharge container 42.

[0118] Specifically, the main fluid filter 10 and the main air filter 20 are kept connected, the container integrity testing device 80 is kept sealed and connected to the first upstream end 21, the first on-off valve 71, the second valve 323, the third valve 171, the fourth valve 172 and the sixth valve 24 are closed, the first valve 13 and the fifth valve 173 are opened, the main air filter 20 is connected to the main fluid filter 10 to the first waste discharge container 42, and the test gas passes through the container integrity testing device 80 in sequence and flows to the main air filter 20, the main fluid filter 10 to the first waste discharge container 42, and then the test gas source is controlled to start pressurizing to a preset value. After reaching the preset value, the pressure is maintained, the pressure drop is detected, and it is determined whether it is qualified.

[0119] 1.2. Top wash bag 16 integrity test steps:

[0120] Keep the main fluid filter 10 and the main air filter 20 connected, keep the container integrity testing device 80 sealed and connected to the first upstream end 21, close the first on-off valve 71, the second valve 323, the fourth valve 172, the fifth valve 173 and the sixth valve 24, open the first valve 13 and the third valve 171, and conduct the flow from the main air filter 20 to the main fluid filter 10 to the top wash bag 16. The test gas passes through the container integrity testing device 80 in sequence and flows to the main air filter 20, the main fluid filter 10 to the top wash bag 16. Then, control the test gas source to start pressurizing to a preset value. After reaching the preset value, maintain the pressure, detect the pressure drop, and determine whether it is qualified.

[0121] The integrity test step of the first row waste container 42 and the integrity test step of the top wash bag 16 may be performed in any order.

[0122] Based on the above test flow path, a low-pressure leakage test step can also be performed. The low-pressure leakage test step is before the container integrity test step:

[0123] Keep the main fluid filter 10 and the main air filter 20 connected, maintain sealed communication between the container integrity test device 80 and the first upstream end 21, close the first on-off valve 71, the second valve 323, the fourth valve 172, and the sixth valve 24, open the first valve 13, the third valve 171, and the fifth valve 173, and conduct the flow from the main air filter 20 to the main fluid filter 10, to the first waste discharge container 42, and to the top wash bag 16. The test gas passes through the container integrity test device 80 in sequence and flows to the main air filter 20, the main fluid filter 10, the first waste discharge container 42, and the top wash bag 16. Then, the test gas source is controlled to begin pressurizing to a preset value. After reaching the preset value, the pressure is maintained, and the pressure drop is detected to determine whether it is qualified (i.e., leakage at the bag body joint is tested).

[0124] A high-pressure leak test step is also included before the low-pressure leak test step, or a high-pressure leak test step is performed directly before the container integrity test step without performing the low-pressure leak test step:

[0125] Keep the main fluid filter 10 and the main air filter 20 connected, keep the filter integrity test device 70 sealed and connected to the first upstream end 21, close the connection between the first upstream part 11, the first downstream part 12, the first upstream end 21, the first downstream end 22 and other components, specifically, close the second valve 323, the third valve 171, the fourth valve 172, the fifth valve 173 and the sixth valve 24, close the opening and closing element 18 on the pipeline connecting the third waste container 14 and the micro-limit sampling bag 15 to the first upstream part 11, open the first on-off valve 71, close the second on-off valve 81, allow the test gas to flow through the filter integrity test device 70 to the main air filter 20 and the main fluid filter 10, and then control the test gas source to start pressurizing to a preset value, maintain the pressure after reaching the preset value, detect the pressure drop, and determine whether it is qualified (i.e., test the leakage of the filter joint).

[0126] 2. Integrity test steps of the main fluid filter 10:

[0127] 2.1. Wetting the main fluid filter 10 and keeping the filter integrity testing device 70 connected to the main air filter 20 and the main fluid filter 10 to perform an integrity test on the main fluid filter 10;

[0128] Specifically, the wetting liquid source is connected to the wetting liquid inlet 321 of the liquid inlet module 30, the second valve 323 is opened, the first valve 13 is closed (if the length of the pipeline between the main fluid filter 10 and the main air filter 20 is long, the first valve 13 can also be left open), the third valve 171, the fourth valve 172 and the fifth valve 173 are closed, the first liquid inlet pump 31 is started, so that the wetting liquid only wets the main fluid filter 10 and does not wet the main air filter 20, and at the same time, the opening and closing element 18 between the first upstream part 11 and the third waste container 14 is opened to connect the two, and the main fluid passes through the first upstream part 11 and the third waste container 14. Exhaust gas from the filter 10 is discharged into the third waste container 14. When wetting liquid flows out of the exhaust port of the main fluid filter 10 and appears in the third waste container 14, the opening and closing element 18 between the first upstream portion 11 and the third waste container 14 is closed, and the first liquid inlet pump 31 is shut down. After a 2-minute standstill, the first liquid inlet pump 31 is restarted, and the fifth valve 173 is opened. The first liquid inlet pump 31 begins to dynamically flush the main fluid filter at a preset speed for 10 minutes. Excess wetting liquid is discharged into the first waste container 42. The main fluid filter 10 is fully wetted.

[0129] 2.2. Testing the main fluid filter 10: Connect the main fluid filter 10 and the main air filter 20, maintain communication between the filter integrity testing device 70 and the first upstream end 21, and pass the test gas through the filter integrity testing device 70, the main air filter 20, and the main fluid filter 10 in sequence to perform an integrity test on the main fluid filter 10;

[0130] Specifically, the filter integrity testing device 70 is connected to the main air filter 20 and opens the first on-off valve 71, opens the first valve 13 and the fifth valve 173, closes the second valve 323, the third valve 171, the fourth valve 172 and the sixth valve 24, and the test gas passes through the filter integrity testing device 70, the main air filter 20 and the main fluid filter 10 in sequence, and the excess test gas is discharged into the first waste container 42, and the integrity of the main fluid filter 10 is tested by the diffusion flow method; when the filter integrity testing device 70 outputs the result, if it passes, proceed to the next step; if it fails, repeat the main fluid filter 10 wetting step, and then perform the main fluid filter 10 testing step again; if it is finally confirmed that there is an integrity problem with the main fluid filter 10, stop the process.

[0131] 3. Main air filter 20 integrity test steps:

[0132] 3.1. Wetting the main air filter 20 until the wetting liquid appears in the second waste container 23, and then maintaining the connection between the filter integrity test device 70 and the main air filter 20 to perform an integrity test on the main air filter 20;

[0133] Specifically, the connection between the main fluid filter 10 and the main air filter 20 is disconnected, the sixth valve 24 is opened, the first on-off valve 71 and the second on-off valve 81 are closed, the wetting liquid source is connected to the second liquid inlet flow path 34, the second liquid inlet pump 33 is started, and the wetting liquid enters from the first upstream end 21 of the main air filter 20 and flows out from the first downstream end 22 to wet the main air filter 20. When the wetting liquid appears in the second waste container 23, it indicates that the main air filter 20 is fully wetted.

[0134] 3.2. Main air filter 20 testing step: disconnect the main fluid filter 10 and the main air filter 20, maintain sealed communication between the filter integrity testing device 70 and the first upstream end 21, and sequentially pass the test gas through the filter integrity testing device 70 and the main air filter 20 to perform an integrity test on the main air filter 20;

[0135] Specifically, the filter integrity testing device 70 is connected to the main air filter 20 and opens the first on-off valve 71, opens the sixth valve 24, closes the second on-off valve 81, and disconnects the connection between the first downstream end 22 and the first upstream portion 11, so that the test gas passes through the filter integrity testing device 70 and the main air filter 20 in turn, and the integrity of the main air filter 20 is tested. The excess test gas is discharged into the second waste container 23. After the filter integrity testing device 70 outputs the result, if it passes, the next step is performed. If it fails, the main air filter 20 wetting step is repeated, and then the main air filter 20 testing step is performed again. If it is finally confirmed that there is an integrity problem with the main air filter 20, the process is stopped.

[0136] 4. Filtration steps:

[0137] Keep the liquid inlet module 30 connected to the main fluid filter 10, and the filtrate passes through the main fluid filter 10 to the liquid outlet module 40 to be filtered, and the filtrate is collected in the liquid outlet module 40;

[0138] Specifically, disconnect the connection between the main fluid filter 10 and the main air filter 20, disconnect the connection between the liquid source and the liquid inlet 322 of the liquid inlet module 30, open the second valve 323, close the first valve 13, the third valve 171, the fourth valve 172 and the fifth valve 173, open the opening and closing element 18 between the first upstream part 11 and the micro-limit sampling bag 15 to connect the two, start the first liquid inlet pump 31 and make it pump the liquid into the micro-limit sampling bag 15 at a preset speed until the preset value is reached, and then stop the first liquid inlet pump 31, sample and measure the properties of the feed liquid, and set the process parameters for subsequent filtration according to the test results; then open the third valve 171, start the first liquid inlet pump 31 and run at a preset speed until the feed liquid in the top wash bag 16 reaches a preset value, and then stop the first liquid inlet pump 31; then open the fourth valve 172, close the third valve 171, start the first liquid inlet pump 31 and run it at the speed set by the process parameters, pump the feed liquid into the main fluid filter 10, start filtration, and collect the filtrate at the product outlet 41.

[0139] 5. Steps for retesting the integrity of the main fluid filter 10:

[0140] The filter integrity testing device 70 is kept in direct connection with the main fluid filter 10 to perform an integrity test on the main fluid filter 10 .

[0141] Specifically, the entire main air filter 20 is removed, the test pipeline of the filter integrity testing device 70 is connected to the first upstream part 11, the first on-off valve 71, the first valve 13 and the fifth valve 173 are opened, the second valve 323, the third valve 171 and the fourth valve 172 are closed, and the opening and closing element 18 on the pipeline connecting the third waste container 14 and the micro-limit sampling bag 15 to the first upstream part 11 is closed, so that the test gas passes through the filter integrity testing device 70 and the main fluid filter 10 in turn, and the integrity of the main fluid filter 10 is tested by the diffusion flow method. After the filter integrity testing device 70 outputs the result, if it passes, the process is completed; if it fails, the main fluid filter 10 wetting step is repeated, and then the main fluid filter 10 integrity retest step is performed.

[0142] The online integrity testing method of the present invention first performs a container integrity test on the filtration system to determine the sealing and integrity of the bag body, thereby avoiding contamination of the filtration system due to bag damage; then performs an integrity test on the main fluid filter 10 and the main air filter 20 to ensure the sealing and sterility of each component before filtering the feed liquid, thereby meeting the sterility requirements of the filtrate, avoiding expensive waste of filtrate, and improving production efficiency; finally, the integrity of the main fluid filter 10 is reviewed to verify the integrity of the entire filtration system during the filtration process to prove the sterility of the filtrate; during this process, the waste gas and wetting liquid discharged from the main fluid filter 10 or the auxiliary fluid filter 50 are input into the corresponding waste discharge container, and the wetting liquid discharged from the main air filter 20 or the auxiliary air filter 60 is input into the corresponding waste discharge container, thereby avoiding backflow contamination of each filter during testing, and also avoiding the wetting liquid, waste gas and test gas being directly discharged into the external environment, thereby ensuring the sterility of the entire filtration system and the external environment.

[0143] like Figure 3 In the second embodiment shown, the filter assembly in the filter system differs from the filter assembly in the first embodiment in that an auxiliary fluid filter 50 and an auxiliary air filter 60 are added, as well as other adaptive modifications. Figure 3 As shown, the auxiliary fluid filter 50 is located upstream of the main fluid filter 10 and is sealed in series in the order of fluid flow. The auxiliary fluid filter 50 includes a second upstream portion 51 and a second downstream portion 52. The second downstream portion 52 is sealed and connected to the first upstream portion 11 or the second upstream portion 51 of another auxiliary fluid filter 50; the waste discharge module also includes a fourth waste discharge container 55 sealed and connected to the second upstream portion 51. The fourth waste discharge container is at least used to receive the waste gas discharged when the auxiliary fluid filter 50 is wetted; the auxiliary fluid filter 50 also needs to undergo integrity testing, and the filtered test gas also needs to pass through the wetted auxiliary fluid filter 50. Therefore, the filter assembly also includes a one-to-one correspondence with the auxiliary fluid filter 50. The auxiliary air filter 60 includes a second upstream end 61 and a second downstream end 62, the second upstream portion 51 is sealedly connected to the second downstream end 62, the waste discharge module also includes a fifth waste discharge container 64 sealedly connected to the second downstream end 62, the liquid inlet module 30 is sealedly connected to the second upstream portion 51 and the second upstream end 61, and can be communicated with the auxiliary fluid filter 50 or the auxiliary air filter 60, the second upstream portion 51 and the second upstream end 61 have an interface that can be sealedly connected to the filter integrity testing device 70 to allow the test gas to pass only through the auxiliary fluid filter 50, or pass through the auxiliary air filter 60 and the auxiliary fluid filter 50 in sequence, or pass through the auxiliary air filter 60 only.

[0144] The test pipeline of the filter integrity test device 70 is connected to the first upstream end 21 and the second upstream end 61 respectively through a three-way solenoid valve 72 , and the flow direction of the test gas is controlled by the three-way solenoid valve 72 .

[0145] Since the auxiliary fluid filter 50 and the auxiliary air filter 60 need to be moistened and the test gas needs to be passed through, and the downstream of the auxiliary fluid filter 50 is another auxiliary fluid filter 50 or the main fluid filter 10, there is no need to additionally seal and set up a waste container, and the same waste container (first waste container 42) can be shared with the main fluid filter 10; and the function of the fourth waste container 55 is similar to that of the third waste container 14. Because there is a lot of air in the auxiliary fluid filter 50, the excess air inside it has a great impact on the auxiliary fluid filter 50. Therefore, during the moistening process, the internal space of the auxiliary fluid filter 50 will gradually be filled with moistening liquid and the waste gas will be discharged from the second upstream part 51. The fourth waste container 55 is sealed and connected to the second upstream part 51. It can receive the waste gas and overflowed moistening liquid discharged when the auxiliary fluid filter 50 is moistened, and serves as a reminder, which is conducive to confirming that the air in the auxiliary fluid filter 50 is completely removed and optimizing the filtering effect. The fifth waste container 64, sealed to the second downstream end 62 of the auxiliary air filter 60, serves the same purpose as the second waste container 23: to ensure the sterility of the test gas filtered by the auxiliary air filter 60 and prevent backflow contamination with the wetting fluid. The interiors of the fourth and fifth waste containers 55 and 64 are both isolated from the outside world, improving the internal sealing and sterility of the filter assembly. They also serve as a reminder when the wetting fluid and test gas flow into the corresponding waste module, guiding the next step. In this embodiment, both the fourth and fifth waste containers 55 and 64 are transparent bags.

[0146] The filtration assembly also includes a micro-sampling bag 15, which is sealedly connected to the second upstream portion 51 of the first auxiliary fluid filter 50 in the fluid flow sequence. The function of the micro-sampling bag 15 is to sample the liquid that has not entered the fluid filter to measure its properties, thereby setting the process parameters for subsequent filtration based on the test results. Generally, the micro-sampling bag 15 is placed upstream of the first fluid filter in the flow direction of the liquid to ensure that unfiltered liquid is collected. When the fluid filtration assembly includes one or more auxiliary fluid filters 50, the micro-sampling bag 15 is sealedly connected to the second upstream portion 51 of the first auxiliary fluid filter 50 in the fluid flow sequence. The micro-sampling bag 15 is not placed on the first upstream portion 11. The fourth waste container 55 and the pipeline connecting the micro-sampling bag 15 to the second upstream portion 51 are each equipped with an opening and closing element 18 to control the connection between the second upstream portion 51 and the fourth waste container 55 and the micro-sampling bag 15.

[0147] Preferably, the liquid inlet module 30 includes a first liquid inlet pump 31 and a first liquid inlet flow path 32, the first liquid inlet flow path 32 has a liquid inlet connected to a wetting liquid source or a feed liquid source, the first liquid inlet pump 31 is arranged on the first liquid inlet flow path 32 to control the fluid flow in the first liquid inlet flow path 32, and the first liquid inlet flow path 32 is sealedly connected to the second upstream part 51 of the first auxiliary fluid filter 50 located in the fluid flow order; the liquid inlet module 30 also includes a second liquid inlet pump 33 and a second liquid inlet flow path 34, the second liquid inlet flow path 34 has a liquid inlet connected to the wetting liquid source, the second liquid inlet pump 33 is arranged on the second liquid inlet flow path 34 to control the fluid flow in the second liquid inlet flow path 34, and the second liquid inlet flow path 34 can be sealed and connected to the first upstream end 21, and when the auxiliary fluid filter 50 has a one-to-one corresponding auxiliary air filter 60, the second liquid inlet flow path 34 can be sealed and connected to the second upstream end 61.

[0148] Specifically, the liquid inlet module 30 is connected to the second upstream part 51, and then the auxiliary fluid filter 50 and the main fluid filter 10 are sequentially passed through the liquid; a seventh valve 53 is provided between the first upstream part 11 and the second downstream part 52, and an eighth valve 54 is provided between the second upstream part 51 and the second downstream end 62; a ninth valve 63 is provided between the fifth waste container 64 connected to the second downstream end 62 and the second downstream end 62.

[0149] Preferably, the liquid inlet includes a wetting liquid inlet 321 and a feed liquid inlet 322 that are independent of each other; when the liquid inlet module 30 includes only one liquid inlet flow path, the liquid inlet flow path includes a wetting liquid inlet 321 and a feed liquid inlet 322 that are independent of each other, and also includes interfaces connected to the main fluid filter 10, the auxiliary fluid filter 50 and the main air filter 20, the auxiliary air filter 60 respectively; when the liquid inlet module 30 includes a first liquid inlet flow path 32 and a second liquid inlet flow path 34, the first liquid inlet flow path 32 is used to transport wetting liquid and feed liquid to the main fluid filter 10 and the auxiliary fluid filter 50, and therefore has independent wetting liquid inlets 321 and feed liquid inlets 322, and the second liquid inlet flow path 34 is used to transport wetting liquid to the main air filter 20 and the auxiliary air filter 60, and therefore has an independent wetting liquid inlet 321.

[0150] Preferably, a first pressure sensor 90 is provided on the first liquid inlet flow path 32 , and the first pressure sensor 90 can be communicatively connected to the control module. The first pressure sensor 90 is capable of detecting the fluid pressure on the first liquid inlet flow path 32. The liquid outlet module 40 includes a liquid outlet flow path connected to the first downstream portion 12, and a second pressure sensor 91 is provided on the liquid outlet flow path. The first pressure sensor 90 and the second pressure sensor 91 are both capable of communicating with the control module. When the filter assembly filters the feed liquid through the auxiliary fluid filter 50 and the main fluid filter 10, the first pressure sensor 90 and the second pressure sensor 91 are respectively located upstream of the auxiliary fluid filter 50 and downstream of the main fluid filter 10. Therefore, by comparing the difference in the values ​​of the first pressure sensor 90 and the second pressure sensor 91, the differential pressure of the feed liquid acting on the main fluid filter 10 and the auxiliary fluid filter 50 can be determined, thereby determining whether the main fluid filter 10 and the auxiliary fluid filter 50 are blocked. If blocked, the staff is promptly notified to replace the entire filter assembly. The feed liquid inlet amount and flow rate in the first liquid inlet flow path 32 can also be controlled to control the differential pressure of the feed liquid within a reasonable range to protect the main fluid filter 10 and the auxiliary fluid filter 50.

[0151] Furthermore, a third pressure sensor 92 is provided between the second downstream portion 52 and the first upstream portion 11. This third pressure sensor 92 is communicatively connected to the control module. By comparing the readings from the third pressure sensor 92 with those from the first pressure sensor 90, the fluid pressure differential experienced by the auxiliary fluid filter 50 can be determined. By comparing the readings from the second pressure sensor 91 with those from the third pressure sensor 92, the fluid pressure differential experienced by the primary fluid filter 10 can be determined. This ensures that differential pressure testing is performed on each fluid filter, increasing accuracy and making it easier to identify a faulty fluid filter.

[0152] Of course, in other embodiments, if the number of auxiliary fluid filters 50 is greater than 1, a pressure sensor may be further provided on the pipeline between two auxiliary fluid filters 50 to protect each fluid filter and promptly determine the blockage status of the fluid filter.

[0153] Based on the filtering system of the second embodiment, the online integrity testing method includes the following steps:

[0154] The fluid filtration system of this embodiment requires the connection of various components such as Figure 3 As shown, the filtrate storage bag is aseptically connected to the product outlet 41;

[0155] The test method is as follows:

[0156] 1. Container integrity test steps: Only the top wash bag 16 and the first row waste container 42 need to be tested for integrity:

[0157] 1.1. First Waste Discharge Container 42 Integrity Test Step: Maintain sealed communication between the container integrity test device and the first upstream end 21, connect the main air filter 20 to the main fluid filter 10 and then to the first waste discharge container 42, and close the communication between the first upstream portion 11 and the first downstream portion 12 and other components. Allow test gas to sequentially pass through the container integrity test device 80 and flow to the main air filter 20, the main fluid filter 10, and then to the first waste discharge container 42, thereby performing an integrity test on the first waste discharge container 42.

[0158] Specifically, the main fluid filter 10 and the main air filter 20 are kept connected, the container integrity testing device 80 is kept sealed and connected to the first upstream end 21, the first on-off valve 71, the seventh valve 53, the third valve 171, the fourth valve 172 and the sixth valve 24 are closed, the first valve 13 and the fifth valve 173 are opened, the main air filter 20 is connected to the main fluid filter 10 to the first waste discharge container 42, and the test gas passes through the container integrity testing device 80 in sequence and flows to the main air filter 20, the main fluid filter 10 to the first waste discharge container 42, and then the test gas source is controlled to start pressurizing to a preset value. After reaching the preset value, the pressure is maintained, the pressure drop is detected, and it is determined whether it is qualified.

[0159] 1.2. Top wash bag 16 integrity test steps:

[0160] Keep the main fluid filter 10 and the main air filter 20 connected, keep the container integrity testing device 80 sealed and connected to the first upstream end 21, close the first on-off valve 71, the seventh valve 53, the fourth valve 172, the fifth valve 173 and the sixth valve 24, open the first valve 13 and the third valve 171, and conduct the main air filter 20 to the main fluid filter 10 to the top wash bag 16. The test gas passes through the container integrity testing device 80 in sequence and flows to the main air filter 20, the main fluid filter 10 to the top wash bag 16. Then, control the test gas source to start pressurizing to a preset value. After reaching the preset value, maintain the pressure, detect the pressure drop, and determine whether it is qualified.

[0161] The integrity test step of the first row waste container 42 and the integrity test step of the top wash bag 16 may be performed in any order.

[0162] Based on the above test flow path, a low-pressure leakage test step can also be performed. The low-pressure leakage test step is before the container integrity test step:

[0163] The main fluid filter 10 and the main air filter 20 are kept connected, and the container integrity testing device 80 is kept in sealed communication with the first upstream end 21. The first on-off valve 71, the seventh valve 53, the fourth valve 172, and the sixth valve 24 are closed. The first valve 13, the third valve 171, and the fifth valve 173 are opened. The main air filter 20 is connected to the main fluid filter 10, and then to the first waste discharge container 42 and the top wash bag 16. The test gas passes through the container integrity testing device 80 in sequence and flows to the main air filter 20, the main fluid filter 10, the first waste discharge container 42, and the top wash bag 16. Then, the test gas source is controlled to begin pressurizing to a preset value. After reaching the preset value, the pressure is maintained, and the pressure drop is detected to determine whether it is qualified (i.e., leakage at the bag body joint is tested).

[0164] Based on the above test flow path, a high-pressure leak test step can be performed before the low-pressure leak test step, or the high-pressure leak test step can be performed directly before the container integrity test step without performing the low-pressure leak test step:

[0165] like Figure 4 As shown, the main fluid filter 10 and the main air filter 20 are kept connected, the auxiliary fluid filter 50 and the auxiliary air filter 60 are kept connected, the filter integrity test device 70 is kept in sealed communication with the second upstream end 61, and the communication between the first upstream portion 11, the first downstream portion 12, the first upstream end 21, the first downstream end 22, the second upstream portion 51, the second downstream portion 52, the second upstream end 61 and the second downstream end 62 and other components is closed, that is, the first on-off valve 71, the second on-off valve 81, the second valve 323, the third valve 171, the fourth valve 172, the fifth valve 173, the sixth valve 24 and the ninth valve 63 are closed, and the third waste container 14 is closed. The opening and closing element 18 on the pipeline connected to the first upstream part 11 closes the fourth waste container 55 and the opening and closing element 18 on the pipeline connecting the micro-limit sampling bag 15 and the second upstream part 51, opens the connection between the three-way solenoid valve 72 and the second upstream end 61, opens the first valve 13, the seventh valve 53 and the eighth valve 54, and the test gas passes through the filter integrity test device 70, the auxiliary air filter 60, and the auxiliary fluid filter 50 in sequence and flows to the main air filter 20 and the main fluid filter 10 respectively, and then controls the test gas source to start pressurizing to a preset value, maintains the pressure after reaching the preset value, detects the pressure drop, and determines whether it is qualified (i.e., the leakage of the test filter joint).

[0166] 2. Fluid filter integrity test steps

[0167] like Figure 4As shown, it specifically includes a fluid filter wetting step. Since the liquid inlet module 30 is connected to the main fluid filter 10 through the auxiliary fluid filter 50, there is also an auxiliary fluid filter 50 wetting step before the main fluid filter 10 wetting step: disconnect the connection between the auxiliary fluid filter 50 and the auxiliary air filter 60, and the wetting liquid enters from the second upstream part 51 of the auxiliary fluid filter 50 and flows out from the second downstream part 52 to wet the auxiliary fluid filter 50; after confirming that the auxiliary fluid filter 50 is wetted, the flow path from the second downstream part 52 to the first upstream part 11 of the main fluid filter 10 is connected to perform the main fluid filter 10 wetting step.

[0168] Specifically, the wetting liquid source is connected to the wetting liquid inlet 321 of the liquid inlet module 30, the second valve 323 is opened, the eighth valve 54 is closed (if the length of the pipeline between the auxiliary fluid filter 50 and the auxiliary air filter 60 is long, the eighth valve 54 can also be left open), the seventh valve 53 is closed, and the first liquid inlet pump 31 is started, so that the wetting liquid only wets the auxiliary fluid filter 50 and does not wet the auxiliary air filter 60. At the same time, the opening and closing element 18 between the second upstream part 51 and the fourth waste container 55 is opened to connect the two, and the exhaust gas inside the auxiliary fluid filter 50 is discharged into the fourth waste container 55. When the wetting liquid flows out of the exhaust port of the auxiliary fluid filter 50, the first When wetting liquid appears in the fourth waste container 55, the opening and closing element 18 between the second upstream portion 51 and the fourth waste container 55 is closed, and the first liquid inlet pump 31 is shut down; after standing for 2 minutes, the first liquid inlet pump 31 is started again, the seventh valve 53 is opened, and the wetting step of the main fluid filter 10 is performed. For details, please refer to Example 1; it should be noted that in this embodiment, based on the connection method of the liquid inlet module 30, the first liquid inlet pump 31 dynamically flushes both the main fluid filter 10 and the auxiliary fluid filter 50; if in other embodiments, the number of auxiliary fluid filters 50 is greater than 1, the above-mentioned wetting steps are also used to wet each auxiliary fluid filter 50 step by step.

[0169] After completing the wetting of the auxiliary fluid filter 50 and the main fluid filter 10, the main fluid filter 10 test step is performed first, the seventh valve 53 is closed, and the connection between the three-way solenoid valve 72 and the first upstream end 21 is opened. For other specific steps, please refer to Example 1. After the integrity of the main fluid filter 10 is passed, the auxiliary fluid filter 50 test step is performed, and the flow path from the second downstream part 52 to the first upstream part 11 of the main fluid filter 10 is connected, the main fluid filter 10 and the main air filter 20 are connected, and the auxiliary fluid filter 50 and the auxiliary air filter 60 are connected, and the filter integrity testing device 70 is kept sealed and connected with the second upstream end 61. The test gas passes through the filter integrity testing device 70, the auxiliary air filter 60, and the auxiliary fluid filter 50 in turn to perform an integrity test on the auxiliary fluid filter 50.

[0170] Specifically, the filter integrity test device 70 is connected to the auxiliary air filter 60 and conducted, the connection between the three-way solenoid valve 72 and the second upstream end 61 is opened, the eighth valve 54, the seventh valve 53, the first valve 13 and the sixth valve 24 are opened, and the first on-off valve 71, the second on-off valve 81, the ninth valve 63, the second valve 323, the third valve 171, the fourth valve 172 and the fifth valve 173 are closed. The test gas passes through the filter integrity test device 70, the auxiliary air filter 60 and the auxiliary fluid filter 50 in sequence. Since the gas mainly flows upward, the test gas flows through the filter integrity test device 70, the auxiliary air filter 60 and the auxiliary fluid filter 50 in sequence. 2 and the fifth valve 173 are both closed, the test gas will not pass through the main fluid filter 10, but will flow through the sixth valve 24 to the second waste container 23 at the first downstream end 22, thereby completing the integrity test of the auxiliary fluid filter 50. The integrity of the auxiliary fluid filter 50 is tested by the diffusion flow method; wait for the filter integrity testing device 70 to output the result. If it passes, proceed to the next step; if it fails, repeat the auxiliary fluid filter 50 wetting step, and then perform the auxiliary fluid filter 50 testing step again; if it is finally confirmed that there is an integrity problem with the auxiliary fluid filter 50, stop the process.

[0171] 3. Air filter integrity test steps

[0172] like Figure 5 As shown, the air filter wetting step specifically includes: disconnecting the communication between the auxiliary fluid filter 50 and the auxiliary air filter 60, opening the sixth valve 24 and the ninth valve 63, closing the first on-off valve 71 and the second on-off valve 81, connecting the wetting liquid source to the second liquid inlet flow path 34, starting the second liquid inlet pump 33, and the wetting liquid enters from the second upstream end 61 of the auxiliary air filter 60 and enters the fifth waste container 64 from the second downstream end 62. The wetting liquid enters from the first upstream end 21 of the main air filter 20 and enters the second waste container 23 from the first downstream end 22. The presence of a preset amount of wetting liquid in the fifth waste container 64 and the second waste container 23 indicates that the auxiliary air filter 60 and the main air filter 20 are fully wetted, respectively.

[0173] Specifically, it includes air filter testing steps: a three-way solenoid valve 72 is provided on the test pipeline of the filter integrity testing device 70 to connect the first upstream end 21 and the second upstream end 61 respectively. The test steps of the main air filter 20 and the auxiliary air filter 60 are in no particular order. The test steps of the main air filter 20 refer to Example 1. The test steps of the auxiliary air filter 60 are as follows: disconnect the connection between the auxiliary fluid filter 50 and the auxiliary air filter 60, close the first on-off valve 71 and the second on-off valve 81, keep the filter integrity testing device 70 sealed and connected with the second upstream end 61, open the ninth valve 63, and the test gas passes through the filter integrity testing device 70 and the auxiliary air filter 60 in turn to perform an integrity test on the auxiliary air filter 60.

[0174] 4. Filtration steps

[0175] like Figure 5 As shown, the connection between the main fluid filter 10 and the main air filter 20 is disconnected, and the connection between the auxiliary fluid filter 50 and the auxiliary air filter 60 is disconnected. The feed liquid passes through the auxiliary fluid filter 50 and the main fluid filter 10 in turn to the liquid outlet module 40 to achieve filtration, and the filtrate is collected in the liquid outlet module 40.

[0176] Specifically, disconnect the connection between the first downstream end 22 and the first upstream portion 11, disconnect the connection between the second downstream end 62 and the second upstream portion 51, disconnect the connection between the liquid source and the liquid inlet 322 of the liquid inlet module 30, open the second valve 323, close the seventh valve 53, the eighth valve 54, the first valve 13, the third valve 171, the fourth valve 172, and the fifth valve 173, open the opening and closing element 18 between the second upstream portion 51 and the micro-limit sampling bag 15, connect the two, start the first liquid inlet pump 31 and pump the liquid into the micro-limit sampling bag 15 at a preset speed until the preset value is reached, and then stop the first liquid inlet pump 31. Pump 31, sample and measure the properties of the feed liquid, and thus set the process parameters for subsequent filtration according to the test results; then open the seventh valve 53 and the third valve 171, and do not operate other valves, start the first liquid inlet pump 31 and run at a preset speed until the feed liquid in the top wash bag 16 reaches a preset value, and then stop the first liquid inlet pump 31; then open the fourth valve 172, close the third valve 171, and do not operate other valves, start the first liquid inlet pump 31 and run at a speed set by the process parameters, pump the feed liquid into the auxiliary fluid filter 50 and the main fluid filter 10 in turn, start filtration, and collect the filtrate at the product outlet 41.

[0177] 5. Fluid filter integrity review steps

[0178] like Figure 6 As shown, the connection between the main fluid filter 10 and the main air filter 20 is disconnected, and the filter integrity test device 70 is kept in sealed communication with the first upstream portion 11. The test gas passes through the filter integrity test device 70 and the main fluid filter 10 in sequence to retest the integrity of the main fluid filter 10.

[0179] Specifically, the entire main air filter 20 is removed, and the test pipeline of the filter integrity test device 70 is connected to the first upstream portion 11. That is, the connection between the three-way solenoid valve 72 and the first upstream portion 11 is opened, the first on-off valve 71, the first valve 13, and the fifth valve 173 are opened, the second on-off valve 81, the second valve 323, the third valve 171, the fourth valve 172, the seventh valve 53, and the eighth valve 54 are closed, and the opening and closing element 18 on the pipeline connecting the third waste discharge container 14 and the micro-limit sampling bag 15 to the first upstream portion 11 is closed. The test gas is then passed through the filter integrity test device 70 and the main fluid filter 10 in sequence, and the integrity of the main fluid filter 10 is tested using the diffusion flow method. After the filter integrity test device 70 outputs a result, if the result is passed, the process is completed. If the result is not passed, the integrity of the auxiliary fluid filter 50 is tested.

[0180] The entire auxiliary air filter 60 is removed, and the test pipeline of the filter integrity test device 70 is connected to the second upstream portion 51. That is, the connection between the three-way solenoid valve 72 and the second upstream portion 51 is opened. The first on-off valve 71, the second on-off valve 81, the second valve 323, the third valve 171, the fourth valve 172, and the fifth valve 173 are closed. The eighth valve 54, the seventh valve 53, and the first valve 13 are opened. The opening and closing element 18 between the first upstream portion 11 of the main fluid filter 10 and the third waste container 14 is opened. This allows the test gas to pass through the filter integrity test device 70 and the auxiliary fluid filter 50 in sequence and flow into the third waste container 14. The integrity of the auxiliary fluid filter 50 is tested using the diffusion flow method. If the test gas passes, the process is terminated. If not, the fluid filter wetting step is repeated, and then the integrity of the main fluid filter 10 and the auxiliary fluid filter 50 is rechecked.

[0181] In other embodiments, the auxiliary fluid filter 50 can use the main air filter 20 to filter the test gas, that is, compared with the filter assembly of Example 1, only the auxiliary fluid filter 50 is added, the second upstream part 51 is sealedly connected to the first downstream end 22, and the liquid inlet module 30 is sealedly connected to the second upstream part 51, and can be connected to the auxiliary fluid filter 50; the second upstream part 51 has an interface for sealing connection to the filter integrity testing device 70, so that the test gas can pass only through the auxiliary fluid filter 50, or pass through the main air filter 20 and the auxiliary fluid filter 50 in sequence; the integrity testing method and filtration steps of the auxiliary fluid filter 50, the main fluid filter 10 and the main air filter 20 in this embodiment can refer to Example 1 and Example 2, and will not be repeated here.

[0182] The above embodiments are only preferred embodiments of the present invention and cannot be used to limit the scope of protection of the present invention. Any non-substantial changes and replacements made by technicians in this field on the basis of the present invention fall within the scope of protection required by the present invention.

Claims

1. A filter assembly comprising a liquid inlet module, a liquid outlet module, a main fluid filter, and a main air filter located upstream of the main fluid filter; The main fluid filter includes a first upstream portion and a first downstream portion, the first downstream portion is sealedly connected to the liquid outlet module, and the main air filter includes a first upstream end and a first downstream end; It is characterized in that The invention also includes a waste discharge module, wherein the waste discharge module includes a first waste discharge container sealedly connected to the liquid outlet module and a second waste discharge container sealedly connected to the first downstream end of the main air filter; The liquid inlet module is sealedly connected to both the first upstream portion and the first upstream end, and is capable of communicating with the main fluid filter or the main air filter. The liquid inlet module has a liquid inlet for connecting to a wetting liquid source or a feed liquid source; The first upstream end and / or the first upstream portion has an interface capable of sealingly communicating with a filter integrity testing device or a container integrity testing device, so as to allow the test gas passing through the filter integrity testing device or the container integrity testing device to pass only through the main air filter, or only through the main fluid filter and then into the first waste container, or pass through the main air filter and the main fluid filter in sequence and then into the first waste container.

2. The filter assembly according to claim 1, wherein The waste discharge module further includes a third waste discharge container sealedly connected to the first upstream portion of the main fluid filter, and the third waste discharge container is at least used to receive waste gas discharged when the main fluid filter is wetted.

3. The filter assembly according to claim 2, wherein The first waste container, the second waste container, and the third waste container are all containers whose initial internal air pressure is zero and whose contents are observable.

4. The filter assembly according to claim 3, wherein The first waste container, the second waste container and the third waste container are all transparent bags.

5. The filter assembly according to any one of claims 1 to 4, characterized in that The system further comprises at least one set of auxiliary fluid filters, the auxiliary fluid filters being located upstream of the main fluid filter and being sealed in series in a fluid flow order, the auxiliary fluid filters comprising a second upstream portion and a second downstream portion, the second downstream portion being sealedly connected to the first upstream portion or the second upstream portion of another auxiliary fluid filter; the waste discharge module further comprising a fourth waste discharge container being sealedly connected to the second upstream portion, the fourth waste discharge container being at least used to receive waste gas discharged when wetting the auxiliary fluid filters; The second upstream portion is sealedly connected to the first downstream end, the liquid inlet module is sealedly connected to the second upstream portion and can communicate with the auxiliary fluid filter; the second upstream portion has an interface for sealing connection to a filter integrity testing device, so that the test gas passing through the filter integrity testing device can pass only through the auxiliary fluid filter, or pass through the main air filter and the auxiliary fluid filter in sequence; or, it further includes a secondary air filter corresponding to the secondary fluid filter one by one, the secondary air filter includes a second upstream end and a second downstream end, the second upstream portion is sealedly connected to the second downstream end, the waste module also includes a fifth waste container sealedly connected to the second downstream end, the liquid inlet module is sealedly connected to both the second upstream portion and the second upstream end, and can communicate with the auxiliary fluid filter or the auxiliary air filter, the second upstream portion and / or the second upstream end has an interface that can be sealedly connected to a filter integrity testing device, so as to allow the test gas passing through the filter integrity testing device to pass only through the secondary fluid filter, or pass through the secondary air filter and the secondary fluid filter in sequence, or pass through the secondary air filter only.

6. The filter assembly according to claim 1, wherein A top wash bag for receiving top wash liquid is provided between the first downstream portion and the liquid outlet module; the interface of the first upstream end is also used to be sealedly connected to the container integrity testing device to allow test gas to pass into the top wash bag.

7. The filter assembly according to claim 1, wherein Also included is a micro-sampling bag sealingly connected to the first upstream portion.

8. The filter assembly according to claim 5, wherein: The invention also includes a micro-limit sampling bag, wherein the micro-limit sampling bag is sealed and connected to the second upstream portion of the first auxiliary fluid filter located in the fluid flow sequence.

9. The filter assembly according to claim 1, wherein: The liquid inlet module includes a first liquid inlet pump and a first liquid inlet flow path, the first liquid inlet flow path has a liquid inlet port connected to a wetting liquid source or a feed liquid source, the first liquid inlet pump is disposed on the first liquid inlet flow path to control the flow of fluid in the first liquid inlet flow path, and the first liquid inlet flow path is sealedly connected to the first upstream portion; The liquid inlet module also includes a second liquid inlet pump and a second liquid inlet flow path, the second liquid inlet flow path has a liquid inlet port connected to the wetting liquid source, the second liquid inlet pump is arranged on the second liquid inlet flow path to control the fluid flow in the second liquid inlet flow path, and the second liquid inlet flow path can be sealed and connected to the first upstream end.

10. The filter assembly according to claim 5, wherein The liquid inlet module includes a first liquid inlet pump and a first liquid inlet flow path, wherein the first liquid inlet flow path has a liquid inlet port connected to a wetting liquid source or a feed liquid source, the first liquid inlet pump is arranged on the first liquid inlet flow path to control the flow of fluid in the first liquid inlet flow path, and the first liquid inlet flow path is sealedly connected to the second upstream portion of the auxiliary fluid filter located first in the fluid flow sequence; The liquid inlet module further includes a second liquid inlet pump and a second liquid inlet flow path, wherein the second liquid inlet flow path has a liquid inlet port connected to a wetting liquid source, and the second liquid inlet pump is disposed on the second liquid inlet flow path to control the flow of fluid in the second liquid inlet flow path, and the second liquid inlet flow path can be sealed and connected to the first upstream end. When the auxiliary fluid filter has a one-to-one correspondence with an auxiliary air filter, the second liquid inlet flow path can be sealed and communicated with the second upstream end.

11. The filter assembly according to claim 9 or 10, characterized in that A first pressure sensor is provided on the first liquid inlet flow path, and the first pressure sensor can be communicatively connected with the control module.

12. The filter assembly according to claim 11, wherein The liquid outlet module includes a liquid outlet flow path connected to the first downstream portion, and a second pressure sensor is provided on the liquid outlet flow path; the first pressure sensor and the second pressure sensor can both be communicatively connected to the control module.

13. The filter assembly according to claim 5, wherein A third pressure sensor is provided between the second downstream portion and the first upstream portion, and the third pressure sensor is communicatively connected to the control module.

14. The filter assembly according to claim 1, 9 or 10, wherein: The liquid inlet comprises a wetting liquid inlet and a feed liquid inlet which are independent of each other; and / or The liquid outlet module includes a product outlet and a waste liquid outlet that are independent of each other, and the waste liquid outlet is sealedly connected to the first waste container.

15. A filtration system, characterized in that: comprising the filter assembly according to any one of claims 1 to 14, further comprising a filter integrity testing device and a container integrity testing device; The filter integrity testing device can be connected to a test gas source to perform integrity testing on the primary fluid filter or the primary air filter or the secondary fluid filter or the secondary air filter; The container integrity testing device can be connected to a test air source to perform an integrity test on the top wash bag or the first waste container and detect the sealing of the flow path from the main air filter to the top wash bag or the first waste container.

16. The filtration system according to claim 15, wherein: A control module is also included to control the execution of the filter integrity test procedure or the filtration procedure or the container integrity test procedure.

17. The filtration system according to claim 16, wherein: It also includes a weight sensing device arranged on the top wash bag, which is communicatively connected to the control module to transmit the amount of material liquid in the top wash bag to the control module. The control module is also used to execute the top wash program based on the amount of material liquid.

18. An online integrity testing method, characterized in that: Using the filtration system according to any one of claims 15 to 17 comprises the following steps:

1. Container integrity test steps: Maintaining sealed communication between the container integrity testing device and the first upstream end, connecting the main air filter to the main fluid filter and then to the first waste container, and closing the communication between the first upstream portion, the first downstream portion and other components, allowing the test gas to sequentially pass through the container integrity testing device and flow to the main air filter, the main fluid filter and then to the first waste container, thereby performing an integrity test on the first waste container; 2. Main fluid filter integrity test steps: Wetting the main fluid filter and keeping the filter integrity testing device connected to the main air filter and the main fluid filter to perform an integrity test on the main fluid filter; 3. Main air filter integrity test steps: Wetting the main air filter until the wetting liquid appears in the second waste container, and then maintaining the filter integrity testing device connected to the main air filter to perform an integrity test on the main air filter; 4. Filtration steps: Keeping the liquid inlet module connected to the main fluid filter, the filtrate passes through the main fluid filter to the liquid outlet module to be filtered, and the filtrate is collected in the liquid outlet module; Main fluid filter integrity retest steps: The filter integrity testing device is kept in direct connection with the main fluid filter to perform an integrity test on the main fluid filter.

19. The method according to claim 18, wherein When the filtration system includes a top wash bag, the method further includes a top wash bag integrity test step: Keep the container integrity testing device sealedly connected to the first upstream end, connect the main air filter to the main fluid filter to the top wash bag, and close the connection between the first upstream part, the first downstream part and other components. The test gas passes through the container integrity testing device in sequence and flows to the main air filter, the main fluid filter and the top wash bag to perform an integrity test on the top wash bag.

20. The method of claim 18, wherein: When the filtration system includes a third waste container, the primary fluid filter integrity testing step includes: disconnecting the main fluid filter from the liquid outlet module, connecting the liquid inlet module to the first upstream portion of the main fluid filter and supplying a wetting liquid to the main fluid filter until the wetting liquid appears in the third waste container, and then stopping the liquid inlet module; After the first preset time, the main fluid filter is connected to the liquid outlet module, the liquid inlet module is started and the main fluid filter is dynamically flushed until the second preset time is reached, the wetting liquid is discharged into the first waste container to achieve complete wetting of the main fluid filter, and then the main fluid filter is subjected to an integrity test.

21. The method of claim 18, wherein: When the filtration system includes a secondary fluid filter, and a fourth waste container is connected to the second upstream portion of the secondary fluid filter, the method further includes a secondary fluid filter integrity testing step: wetting the secondary fluid filter until wetting liquid appears in the fourth waste container, and maintaining the filter integrity testing device connected to the secondary fluid filter via the main air filter or the secondary air filter to perform an integrity test on the secondary fluid filter; and / or When the filtration system includes a secondary air filter, and the second downstream end of the secondary air filter is sealedly connected to a fifth waste container, the method further includes a secondary air filter integrity testing step: wetting the secondary air filter until a wetting liquid appears in the fifth waste container, and then maintaining the filter integrity testing device connected to the secondary air filter to perform an integrity test on the secondary air filter; and / or When a micro-limit sampling bag is connected to the upstream part of the first main fluid filter or auxiliary fluid filter located in the fluid flow sequence, the filtration step also includes: controlling the liquid inlet module to be connected to the first main fluid filter or auxiliary fluid filter located in the fluid flow sequence, and starting the liquid inlet module until the liquid entering the micro-limit sampling bag reaches a preset value, and then stopping the liquid inlet module.

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