CN114713037B - Online filter membrane integrity testing device and method and application thereof - Google Patents
Online filter membrane integrity testing device and method and application thereof Download PDFInfo
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- CN114713037B CN114713037B CN202210649809.1A CN202210649809A CN114713037B CN 114713037 B CN114713037 B CN 114713037B CN 202210649809 A CN202210649809 A CN 202210649809A CN 114713037 B CN114713037 B CN 114713037B
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Abstract
The invention provides an online filter membrane integrity testing device, an online filter membrane integrity testing method and application, which are used for online filter membrane integrity testing in radioactive liquid medicine production, and the online filter membrane integrity testing device comprises: the two port filters that connect, detachably set up on the production line of radioactive liquid medicine includes: a first communication port configured to introduce a radioactive liquid medicine or a pressurized gas into the dual communication port filter; the second communication port is communicated with the first communication port; and an outlet configured to discharge the radioactive liquid medicine or the pressurized gas from the dual communication port filter, a gas filter connected to the second communication port through the communication pipe, the communication pipe being provided with a switching valve configured to be in a closed state when performing a membrane integrity test; and a first three-way valve and a second three-way valve which are respectively arranged at two sides of the filter with the double communication ports.
Description
Technical Field
The invention relates to the technical field of medicines, in particular to an online filter membrane integrity testing device and method and application thereof.
Background
Radioactive liquid medicine has strong radiation, and production needs to be operated in a shielding isolation box. Due to the short half-life of radionuclides, production is generally performed fully automatically in dedicated synthesis modules. The method for producing the radioactive liquid medicine by adopting the shielding isolation box comprises the steps of placing the synthesis module in the shielding isolation box, filling raw material consumables such as chemical reagents and the like into the automatic synthesis module, closing the shielding door, injecting radioactive raw materials into the automatic synthesis module through a special shielding pipeline and starting production, and conveying products to product bottles for split charging after full-automatic synthesis. After production is finished, the nuclide decays to the state that the shielding door can be opened (generally, the operation is carried out after 10 half-lives), equipment cleaning is carried out, and the next production is carried out.
Carry the product bottle at the product and carry out the partial shipment before using, need filter the product, when carrying out the test of filter membrane integrality, often need dismantle out its integrality of off-line measuring with filter membrane, influenced production efficiency greatly.
Disclosure of Invention
Some embodiments of the present invention provide an in-line filter membrane integrity testing apparatus for in-line filter membrane integrity testing in the production of radioactive pharmaceutical fluids, the in-line filter membrane integrity testing apparatus comprising:
the two port filters that connect, detachably set up on the production line of radioactive liquid medicine includes:
a first communication port configured to introduce a radioactive liquid medicine or a pressurized gas into the dual communication port filter;
the second communication port is communicated with the first communication port; and
an outlet configured to discharge the radioactive liquid medicine or the pressurized gas from the dual communication port filter,
the gas filter is connected with the second communication port through the communication pipe, a switch valve is arranged on the communication pipe, and the switch valve is configured to be in a closed state when an online filter membrane integrity test is executed; and
first three-way valve and second three-way valve set up respectively the both sides of two-way mouth filter, the first end of first three-way valve and second end connect respectively the feed liquor pipe with the first connection mouth of two-way mouth filter, the intake pipe is connected to the third end of first three-way valve, the first end and the second end of second three-way valve are connected respectively the export and the drain pipe of two-way mouth filter, the outlet duct is connected to the third end of second three-way valve.
In some embodiments, the first three-way valve is configured to switch between a first state and a second state, the second three-way valve is configured to switch between a third state and a fourth state,
when the first three-way valve is in a first state and the second three-way valve is in a third state, the liquid inlet pipe, the dual-connection port filter and the liquid outlet pipe form a passage so that the radioactive liquid medicine flows through the passage to filter bacteria;
when first three-way valve is located the second state just when the second three-way valve is located the fourth state, the intake pipe intercommunication the first mouth of doubly-linked mouth filter the outlet duct intercommunication the export of doubly-linked mouth filter to realize online filter membrane integrality test.
In some embodiments, the dual port filter comprises:
a first housing;
a liquid filtering membrane disposed inside the first housing, dividing the inside of the first housing into a first cavity and a second cavity, the liquid filtering membrane configured to allow liquid to pass therethrough and remove bacteria in the liquid;
the first connecting pipe extends from the first shell and is communicated with the first cavity, and the first communication port and the second communication port are arranged on the first connecting pipe; and
and the second connecting pipe extends from the first shell and is communicated with the second cavity, and the outlet is arranged on the second connecting pipe.
In some embodiments, the first connection tube comprises:
the first sub-pipe extends from the first shell along the direction far away from the first cavity and is communicated with the first cavity, and the first communication port is arranged at the end part of the first sub-pipe far away from the first shell; and
and the second sub-pipe extends from the middle part of the first sub-pipe along the direction which is basically vertical to the first sub-pipe and is communicated with the first sub-pipe, and the second communication port is arranged at the end part of the second sub-pipe, which is far away from the first sub-pipe.
In some embodiments, the dual port filter comprises:
a first housing;
a liquid filtering membrane disposed inside the first housing, dividing the inside of the first housing into a first cavity and a second cavity, the liquid filtering membrane configured to allow liquid to pass therethrough and remove bacteria in the liquid;
the third connecting pipe extends from the first shell and is communicated with the first cavity, and the first communication port is arranged on the third connecting pipe;
a fourth connecting pipe extending from the first housing and communicating with the first cavity, the second communicating port being provided on the fourth connecting pipe,
and
and the second connecting pipe extends from the first shell and is communicated with the second cavity, and the outlet is arranged on the second connecting pipe.
In some embodiments, the gas filter comprises:
a second housing;
and the gas filtering membrane is arranged in the second shell and divides the second shell into a third cavity and a fourth cavity, and the gas filtering membrane is configured to allow gas to pass and prevent liquid from passing.
In some embodiments, at least a portion of the in-line integrity testing device is disposed within a shielded isolation box.
The invention provides an online filter membrane integrity testing method, which utilizes the online filter membrane integrity testing device of the embodiment and comprises the following steps:
switching the first three-way valve to a first state and the second three-way valve to a third state, opening the switch valve, allowing the pressurized liquid medicine to flow through the liquid inlet pipe, enter the double-connection-port filter through the first connection port, filter and discharge the liquid medicine through the liquid outlet pipe; and
and switching the first three-way valve to a second state and switching the second three-way valve to a fourth state, closing the switch valve, and allowing the test gas to enter the double-communication-port filter through the gas inlet pipe to perform an online filter membrane integrity test.
In some embodiments, prior to switching the first three-way valve to the second state and the second three-way valve to the fourth state, and closing the on-off valve, the in-line filter membrane integrity test method further comprises:
and flushing the double-communication-port filter with water for injection to infiltrate the liquid filtering membrane in the double-communication-port filter.
The invention provides a use of the in-line filter membrane integrity test device according to the preceding embodiment in an in-line filter membrane integrity test.
Compared with the related art, the invention has at least the following technical effects:
the online filter membrane integrity test in the radioactive liquid medicine production is realized by adopting the double-communication-port filter and the gas filter which are arranged on the radioactive liquid medicine production line and the communication pipe which connects the double-communication-port filter and the gas filter and is provided with the switch valve, so that the production and test efficiency is improved. The problem that the pressed gas cannot be discharged in the process of filtering liquid medicine due to the adoption of a conventional sterile filter is solved, the problem that the integrity of the filter membrane of the exhaust filter cannot be tested by adopting a foaming method in the related technology is solved, and the complicated flow caused by the fact that the filter needs to be dismantled from a production line when the integrity of the filter membrane is tested in the related technology is avoided.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and those skilled in the art can also obtain other drawings according to the drawings without creative efforts.
FIG. 1 is a schematic diagram of an in-line filter integrity testing apparatus according to some embodiments of the present invention;
FIG. 2 is a schematic diagram of a partial explosion structure of the in-line filter membrane integrity testing apparatus of FIG. 1;
FIG. 3 is a schematic view of the dual port filter of FIG. 1;
FIG. 4 is a schematic view of the gas filter of FIG. 1;
FIG. 5 is a schematic diagram of another dual port filter according to some embodiments of the present invention; and
FIG. 6 is a flow chart of an in-line filter integrity testing method according to some embodiments of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention will be described in further detail with reference to the accompanying drawings. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The terminology used in the embodiments of the invention is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used in the description of the invention and the appended claims, the singular forms "a", "an", and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise, and "the plural" typically includes at least two.
It should be understood that the term "and/or" as used herein is merely one type of association that describes an associated object, meaning that three relationships may exist, e.g., a and/or B may mean: a exists alone, A and B exist simultaneously, and B exists alone. In addition, the character "/" herein generally indicates that the former and latter related objects are in an "or" relationship.
It is also noted that the terms "comprises," "comprising," or any other variation thereof, are intended to cover a non-exclusive inclusion, such that an article or apparatus that comprises a list of elements does not include only those elements but may include other elements not expressly listed or inherent to such article or apparatus. Without further limitation, the recitation of an element by the phrase "comprising a" does not exclude the presence of additional like elements in a commodity or device comprising the element.
In the related art, radioactive liquid medicine has strong radiation, and production needs to be performed in a shielded and isolated box, which is called a hot chamber. Due to the short half-life of radionuclides, production is generally performed fully automatically in dedicated synthesis modules. The method for producing the radioactive liquid medicine by adopting the hot chamber comprises the steps of placing the synthesis module in the hot chamber, filling raw material consumables such as chemical reagents and the like into the automatic synthesis module, closing the shielding door, injecting radioactive raw materials into the automatic synthesis module through a special shielding pipeline, starting production, conveying the product to a product bottle after full-automatic synthesis, and subpackaging for use.
Production of radioactive pharmaceutical solutions typically involves a sterilization process, typically a sterile filtration process, requiring filter membrane integrity testing of the sterile filter in the hot room immediately after production is complete. Since the inside of the hot chamber and the sterilizing filter still have a strong radioactive dose after the production is finished. In the related art, it is often necessary to take the sterilizing filter out of the production line and perform off-line filter integrity tests, for example, by using a foaming process. Thus, a process is complicated, which easily causes leakage of radioactive materials.
In the related art, the aseptic filtration production process generally employs a conventional filter, whereas in the aseptic filtration production process, sterilization is generally performed by pushing a radioactive liquid medicine to be transferred through a sterile filtration membrane in the filter with a positive gas pressure. In this case, the radioactive liquid medicine is contaminated with gas, and the ordinary aseptic filter cannot discharge the gas that has been pushed in, and cannot effectively filter the radioactive liquid medicine, for example, it is difficult to filter the liquid medicine.
In order to solve the above problems, the present invention provides an in-line filter membrane integrity testing apparatus for in-line filter membrane integrity testing in radioactive liquid medicine production, comprising: the two port filters that connect, detachably set up on the production line of radioactive liquid medicine includes: a first communication port configured to introduce a radioactive liquid medicine or a pressurized gas into the dual communication port filter; the second communication port is communicated with the first communication port; and an outlet configured to discharge the radioactive liquid medicine or the pressurized gas from the dual communication port filter, a gas filter connected to the second communication port through the communication pipe, the communication pipe being provided with a switching valve configured to be in a closed state when performing a membrane integrity test; first three-way valve and second three-way valve set up respectively the both sides of two-way mouth filter, the first end of first three-way valve and second end connect respectively the feed liquor pipe with the first one-way mouth of two-way mouth filter, the intake pipe is connected to the third end of first three-way valve, the first end and the second end of second three-way valve are connected respectively the export and the drain pipe of two-way mouth filter, the outlet duct is connected to the third end of second three-way valve. The online filter membrane integrity test in the radioactive liquid medicine production is realized by adopting the double-communication-port filter and the gas filter which are arranged on the radioactive liquid medicine production line and the communication pipe which connects the double-communication-port filter and the gas filter and is provided with the switch valve, so that the production and test efficiency is improved.
Alternative embodiments of the present invention are described in detail below with reference to the accompanying drawings.
FIG. 1 is a schematic diagram of an in-line filter integrity testing apparatus according to some embodiments of the present invention; FIG. 2 is a schematic diagram of a partial explosion structure of the in-line filter membrane integrity testing apparatus of FIG. 1; FIG. 3 is a schematic view of the dual port filter of FIG. 1; fig. 4 is a schematic view showing the structure of the gas filter of fig. 1.
As shown in fig. 1-4, some embodiments of the present invention provide an in-line filter integrity testing apparatus 100 for in-line filter integrity testing in the production of radiopharmaceutical solutions. At least a portion of the in-line filter integrity testing apparatus 100 is disposed, for example, within a shielded isolation box 200 to shield the radiopharmaceutical liquid from radiation as much as possible and to prevent radionuclide leakage during the manufacturing process.
As shown in fig. 1 to 4, the in-line filter membrane integrity testing apparatus includes a dual communication port filter 10 and a gas filter 20.
The duplex port filter 10 is detachably provided on the production line of the radioactive liquid medicine, and the duplex port filter 10 includes a first communication port 13, a second communication port 14, and an outlet 15. The first communication port 13 is configured to introduce a radioactive drug solution or a pressurized gas into the duplex port filter 10, and when the duplex port filter 10 performs a bacteria filtering operation on the radioactive drug solution on a production line of the radioactive drug solution, the pressurized radioactive drug solution enters the duplex port filter 10 through the first communication port 13, and when the duplex port filter 10 performs an on-line membrane integrity test, the pressurized gas enters the duplex port filter 10 through the first communication port 13.
The second communication port 14 communicates with the first communication port 13, both of which communicate with the same chamber, for example, the first chamber a, inside the dual communication port filter 10. The outlet 15 is configured to discharge the radioactive liquid medicine or the pressurized gas from the dual communication port filter 10.
The gas filter 20 is connected to the second communication port 14 through the communication pipe 90, and a switch valve 91 is disposed on the communication pipe 90, and the switch valve 91 is configured to be in a closed state when performing a membrane integrity test, and to be in an open state when performing a filtration sterilization of the radioactive liquid medicine.
The filter 10 and the gas filter 20 are detachably disposed on the production line of the radioactive liquid medicine, so as to facilitate the replacement of the filter 10 and the gas filter 20, and in some embodiments, the filter 10 and the gas filter 20 may be used for filtering one or more batches of radioactive liquid medicine, and when the usage time limit is reached or different batches of liquid medicine are produced, the filter 10 and the gas filter 20 need to be replaced.
The on-line filter membrane integrity testing device 100 includes a first three-way valve 30 and a second three-way valve 40, and the first three-way valve 30 and the second three-way valve 40 are respectively disposed at both sides of the dual communication port filter 10.
The first end 31 and the second end 32 of the first three-way valve 30 are respectively connected with the liquid inlet pipe 51 and the first communication port 13 of the dual-communication-port filter 10, and the third end 33 of the first three-way valve 30 is connected with the air inlet pipe 61. The first three-way valve 30 is switchable between a first state and a second state, when the first three-way valve 30 is in the first state, a passage is formed between the first end 31 and the second end 32 inside the first three-way valve 30, and the third end 33 is not communicated with the first end 31 and the second end 32; when the first three-way valve 30 is in the second state, a passage is formed between the second end 32 and the third end 33 inside the first three-way valve 30, and the first end 31 is not communicated with the second end 32 and the third end 33.
The first end 41 and the second end 42 of the second three-way valve 40 are respectively connected to the outlet 15 and the liquid outlet 52 of the two-way filter 10, and the third end 43 of the second three-way valve 40 is connected to the gas outlet 62. The second three-way valve 40 can be switched between a third state and a fourth state, when the second three-way valve 40 is in the third state, a passage is formed between the first end 41 and the second end 42 inside the second three-way valve 40, and the third end 43 is not communicated with the first end 41 and the second end 42; when the second three-way valve 40 is in the fourth state, a passage is formed between the first end 41 and the third end 43 inside the second three-way valve 40, and the second end 42 is not communicated with the first end 41 and the third end 43.
In some embodiments, when the first three-way valve 30 is in the first state and the second three-way valve is in the third state, the liquid inlet pipe 51, the dual-port filter 10 and the liquid outlet pipe 52 form a passage so that the radioactive liquid medicine flows through the passage to filter bacteria, and the on-off valve 91 of the communication pipe 90 is in an open state to communicate the second communication hole of the dual-port filter 10 and the gas filter 20, so that the gas entering the dual-port filter 10 can be smoothly discharged during the sterilization and filtration of the radioactive liquid medicine.
When the first three-way valve 30 is in the second state and the second three-way valve 40 is in the fourth state, the air inlet pipe 61 is communicated with the first communication port 13 of the two-communication port filter and the air outlet pipe 62 is communicated with the outlet 15 of the two-communication port filter 10, so that the online filter membrane integrity test is realized.
In some embodiments, as shown in fig. 3, the dual port filter 10 includes a first housing 11 and a liquid filtering membrane 12 disposed inside the first housing 11. The first housing 11 is made of, for example, a polymer material, for example, one or more selected from polyether ether ketone (PEEK), silicone, Polytetrafluoroethylene (PTFE), Polyethylene (PE), polypropylene (PP), Perfluoroalkoxy (PFA), polyvinyl chloride (PVC), Polyimide (PI), and Fluorinated Ethylene Propylene (FEP).
The liquid filtration membrane 12 is, for example, a sterile filtration membrane, and a hydrophilic membrane layer may be used. The liquid filtering membrane 12 is disposed inside the first housing 11, and divides the inside of the first housing 11 into a first cavity a and a second cavity B, and the liquid filtering membrane 12 is configured to allow the liquid to pass therethrough and remove bacteria in the liquid.
As shown in fig. 3, the dual port filter 10 further includes a first connection pipe 16 and a second connection pipe 17 respectively disposed at both sides of the first housing 11. A first connecting pipe 16 extends from the first housing 11 and is communicated with the first cavity a, and the first communication port 13 and the second communication port 14 are arranged on the first connecting pipe 16; a second connecting pipe 17 extends from the first housing 11 and communicates with the second cavity B, and the outlet 15 is disposed on the second connecting pipe 17, for example, at an end of the second connecting pipe 17 away from the first housing 11.
In some embodiments, as shown in fig. 3, the first connection pipe 16 includes a first sub-pipe 161 and a second sub-pipe 162, the first sub-pipe 161 extends from the first shell 11 in a direction away from the first cavity a and is communicated with the first cavity a, and the first communication port 13 is disposed at an end of the first sub-pipe 161 away from the first shell 11; the second sub-pipe 162 extends from the middle of the first sub-pipe 161 in a direction substantially perpendicular to the first sub-pipe 161, and communicates with the first sub-pipe 161, and the second communication port 14 is provided at an end of the second sub-pipe 162 away from the first sub-pipe 161.
Fig. 5 shows a schematic structural diagram of another dual-port filter provided by some embodiments of the present invention, and as shown in fig. 5, the dual-port filter 10 includes a first housing 11 and a liquid filtering membrane 12 disposed inside the first housing 11. The first housing 11 is made of, for example, a polymer material, for example, one or more selected from polyether ether ketone (PEEK), silicone, Polytetrafluoroethylene (PTFE), Polyethylene (PE), polypropylene (PP), Perfluoroalkoxy (PFA), polyvinyl chloride (PVC), Polyimide (PI), and Fluorinated Ethylene Propylene (FEP).
The liquid filtration membrane 12 is, for example, a sterile filtration membrane, and a hydrophilic membrane layer may be used. The liquid filtering membrane 12 is disposed inside the first housing 11, and divides the inside of the first housing 11 into a first cavity a and a second cavity B, and the liquid filtering membrane 12 is configured to allow the liquid to pass therethrough and remove bacteria in the liquid.
As shown in fig. 5, the dual port filter 10 further includes third and fourth connection pipes 18 and 19 and a second connection pipe 17. The third and fourth connection pipes 18 and 19 and the second connection pipe 17 are respectively disposed at both sides of the first housing 11. A third connecting pipe 18 extends from the first housing 11 and is communicated with the first cavity a, and the first communicating opening 13 is disposed on the third connecting pipe 18, for example, at an end of the third connecting pipe 18 far from the first housing 11. A fourth connecting pipe 19 extends from the first housing 11 and is communicated with the first cavity a, and the second communicating port 14 is disposed on the fourth connecting pipe 19, for example, at an end of the fourth connecting pipe 19 far away from the first housing 11. A second connection pipe 17 extends from the first housing 11 and communicates with the second chamber B, and the outlet 15 is provided on the second connection pipe 17. For example at the end of the second connecting tube 17 remote from the first housing 11.
In some embodiments, as shown in fig. 1 to 4, the gas filter 20 includes a second housing 21 and a gas filtering membrane 22 disposed inside the second housing 21. The second housing 21 is made of, for example, a polymer material, for example, one or more selected from polyether ether ketone (PEEK), silicone, Polytetrafluoroethylene (PTFE), Polyethylene (PE), polypropylene (PP), Perfluoroalkoxy (PFA), polyvinyl chloride (PVC), Polyimide (PI), and Fluorinated Ethylene Propylene (FEP).
A gas filtering membrane 22, which may be, for example, a hydrophobic membrane layer configured to allow gas to pass therethrough and prevent liquid from passing therethrough, is disposed inside the second housing 21 to divide the inside of the second housing into a third cavity C and a fourth cavity D.
The gas filter 20 further includes an inlet 23 and an exhaust port 24 respectively disposed at two sides of the gas filtering membrane 22, the inlet 23 is communicated with the third cavity C, the exhaust port 24 is disposed on the second housing 21, for example, and is communicated with the fourth cavity and the outside, and in some embodiments, a mesh structure is disposed in the exhaust port 24, for example, to ensure gas circulation and protect the gas filtering membrane 22 in the gas filter 20.
In the aseptic filtration production process of radioactive liquid medicine, the sterilization is generally performed by using a gas, such as an inert gas, such as nitrogen, etc., and pushing the radioactive liquid medicine to transfer and flow through a sterile filtration membrane in a filter assembly under positive pressure. When the first three-way valve 30 is switched to the first state and the second three-way valve 40 is switched to the third state, the on-off valve 91 on the communication pipe 90 is in the open state, the pressurized radioactive liquid medicine carrying gas enters the dual-port filter 10 through the first communication port 13 of the dual-port filter 10, for example, enters the first cavity a of the dual-port filter 10, the liquid filtering membrane 12 allows the radioactive liquid medicine to pass through due to its hydrophilicity, so as to prevent the gas from passing through, and the liquid filtering membrane 12 can filter out bacteria of the radioactive liquid medicine. The gas filtering membrane 22 allows gas to pass through but prevents liquid from passing through due to its hydrophobicity. Under the action of the pressure in the first chamber a, the radioactive liquid medicine flows through the liquid filtering membrane 12 to perform the sterilization operation and enters the second chamber B, and then enters the liquid outlet pipe 52 through the outlet 15 of the dual port filter 10. The gas in the first chamber a enters the gas filter 20 through the second communication port 14 and the communication pipe 90, and is discharged to the outside from the exhaust port 24 through the gas filtering membrane 22.
Compared with the single sterile filter, the filter with the double connecting ports and the gas filter can effectively discharge gas pressed into the filter assembly, and effective filtering in radioactive liquid medicine production is achieved.
When the first three-way valve 30 is switched to the second state and the second three-way valve 40 is switched to the fourth state, the air inlet pipe 61 is communicated with the first communication port 13 of the two-communication port filter 10, the outlet 15 of the two-communication port filter 10 is communicated with the air outlet pipe 62, and the on-off valve 91 on the communication pipe 90 is in the closed state, at this time, the two-communication port filter 10 is not communicated with the gas filter 20, which can be regarded as a common sterile filter, and the integrity test can be performed by adopting a conventional filter membrane integrity test method, such as a foaming method.
Through switching the state of first three-way valve 30 and second three-way valve 40 and the state of ooff valve 91, can accomplish the test of filter membrane integrality on line, need not tear the filter membrane integrality test that can accomplish two continuous port filters 10 from the production line down, accomplish the test of filter membrane integrality promptly on line, improved production efficiency.
In some embodiments, as shown in fig. 1-4, the in-line filter integrity testing apparatus 100 further comprises a radioactive drug fluid pressurization device 71 connected to an end of the inlet tube 51 remote from the dual port filter 10 for supplying a pressurized radioactive drug fluid. The radiopharmaceutical pressurizing apparatus 71 may supply a high-pressure radiopharmaceutical, for example, by pressurizing with a gas. The radioactive liquid medicine pressurizing device 71 can be placed in the shielding isolation box 200 or outside the shielding isolation box 200, when the radioactive liquid medicine pressurizing device is placed in the shielding isolation box 200, the liquid inlet pipe 51 is completely positioned in the shielding isolation box 200, when the radioactive liquid medicine pressurizing device 71 is placed outside the shielding isolation box 200, the liquid inlet pipe 51 penetrates through the wall of the shielding isolation box 200 to be connected with the radioactive liquid medicine pressurizing device 71, and a sealing member is arranged at the penetrating position to ensure the tightness of the shielding isolation box 200.
In some embodiments, as shown in fig. 1-4, the in-line filter integrity testing device 100 further comprises a sterilized medical fluid collection container 72 connected to the end of the outlet conduit 52 remote from the dual port filter 10 for collecting the sterilized radioactive medical fluid. The sterilization liquid medicine collecting container 72 may collect the radioactive liquid medicine from which bacteria have been filtered out. Degerming liquid medicine collection container 72 can place in shielding shielded box 200, also can place outside shielding shielded box 200, when degerming liquid medicine collection container 72 placed in shielding shielded box 200, drain pipe 52 is located shielding shielded box 200 completely, when degerming liquid medicine collection container 72 placed outside shielding shielded box 200, drain pipe 52 pierces through the wall of shielding shielded box 200 and is connected with degerming liquid medicine collection container 72, set up the leakproofness that the sealing member guaranteed shielding shielded box 200 in the department that pierces through.
In some embodiments, as shown in fig. 1-4, the in-line filter membrane integrity testing apparatus 100 further comprises a gas source 81 connected to an end of the gas inlet tube 61 remote from the dual port filter 10 for supplying pressurized gas for in-line filter membrane integrity testing. The gas source 81 may provide a gas for membrane integrity testing, such as nitrogen, and may regulate the gas pressure. The air source 81 can be placed in the shielding isolation box 200 or outside the shielding isolation box 200, when the air source is placed in the shielding isolation box 200, the air inlet pipe 61 is completely located in the shielding isolation box 200, when the air source 81 is placed outside the shielding isolation box 200, the air inlet pipe 61 penetrates through the wall of the shielding isolation box 200 to be connected with the air source 81, and a sealing member is arranged at the penetrating position to ensure the tightness of the shielding isolation box 200.
In some embodiments, as shown in fig. 1-4, the in-line filter integrity testing apparatus 100 further comprises a gas detection device 82 connected to an end of the outlet tube 62 remote from the dual port filter 10 for detecting a change in gas pressure. The gas detection device 82 can be placed in the shielding isolation box 200 or outside the shielding isolation box 200, when the gas detection device 200 is placed in the shielding isolation box 200, the gas outlet pipe 62 is completely positioned in the shielding isolation box 200, when the gas detection device 82 is placed outside the shielding isolation box 200, the gas outlet pipe 62 penetrates through the wall of the shielding isolation box 200 to be connected with the gas detection device 82, and a sealing piece is arranged at the penetrating position to ensure the tightness of the shielding isolation box 200.
The connection of above-mentioned each part adopts luer to connect for example, and convenient the dismantlement just avoids revealing.
When the first three-way valve 30 is switched to the first state and the second three-way valve 40 is switched to the third state, and the on-off valve 91 on the communication pipe 90 is in the open state, the liquid inlet pipe 51, the two-way filter 10 and the liquid outlet pipe 52 form a passage so that the radioactive liquid medicine flows through the passage to filter bacteria. At this time, the high-pressure radioactive drug solution from the radioactive drug solution pressurizing device 71 passes through the duplex port filter 10 to remove bacteria, and is collected in the sterilizing drug solution collecting container 72 through the liquid outlet pipe 52, thereby realizing the production of sterile drug solution.
When the first three-way valve 30 is switched to the second state and the second three-way valve 40 is switched to the fourth state, and the on-off valve 91 on the communication pipe 90 is in the closed state, the air inlet pipe 61 is communicated with the first communication port 13 of the two-communication port filter 10, and the air outlet pipe 62 is communicated with the outlet 15 of the two-communication port filter 10, so as to realize the online filter membrane integrity test. For example, in the bubbling method, a gas such as nitrogen is supplied from the gas source 81 through the gas supply pipe 61 to the two-port filter 10, and the pressure of the gas is gradually increased until the gas detection device 82 detects a change in the gas pressure. At this time, if the pressure of the gas provided by the gas source 81 is greater than or equal to the predetermined value, it is indicated that the liquid filtering membrane 12 in the dual-port filter 10 is intact, and the radioactive liquid medicine collected into the sterilizing liquid medicine collecting container 72 is satisfactory; if the pressure of the gas supplied from the gas source 81 is less than the predetermined value, it is determined that the liquid filtering membrane 12 of the dual port filter 10 is broken and the radioactive medical fluid collected in the sterilizing medical fluid collecting container 72 is not satisfactory.
Fig. 6 is a flow chart of an in-line filter membrane integrity testing method according to some embodiments of the present invention, and as shown in fig. 6, some embodiments of the present invention provide an in-line filter membrane integrity testing method, which may include the following steps using the in-line filter membrane integrity testing apparatus according to the previous embodiments:
s601: and switching the first three-way valve to a first state and switching the second three-way valve to a third state, opening the switch valve, enabling the pressurized liquid medicine to flow through the liquid inlet pipe, enter the filter with the double connecting ports through the first connecting port, filter and discharge the liquid medicine through the liquid outlet pipe.
S603: and switching the first three-way valve to a second state and switching the second three-way valve to a fourth state, closing the switch valve, and allowing the test gas to enter the double-communication-port filter through the gas inlet pipe to perform an online filter membrane integrity test.
Specifically, the switching control of the first three-way valve, the second three-way valve, and the on-off valve may be electronically controlled or mechanically controlled, as long as the two are switched substantially simultaneously.
In some embodiments, as shown in fig. 6, prior to switching the first three-way valve to the second state and the second three-way valve to the fourth state, and closing the on-off valve, the in-line filter membrane integrity test method further comprises:
s602: flushing the dual port filter with water for injection to infiltrate the liquid filtration membrane in the dual port filter.
Specifically, when the flow path of the radioactive liquid medicine is flushed with the injection water, the radioactive liquid medicine in the duplex port filter 10 is flushed clean when the duplex port filter 10 performs online filter membrane detection, and the liquid filter membrane 12 of the duplex port filter 10 is infiltrated with the injection water, so that a more accurate test result can be obtained when a filter membrane integrity test is performed by adopting a bubbling method.
Some embodiments of the invention also provide for the use of an in-line filter membrane integrity test apparatus according to the preceding embodiments in an in-line filter membrane integrity test.
The flowchart and block diagrams in the figures illustrate the architecture, functionality, and operation of possible implementations of systems, methods and computer program products according to various embodiments of the present invention. In this regard, each block in the flowchart or block diagrams may represent a module, segment, or portion of code, which comprises one or more executable instructions for implementing the specified logical function(s). It should also be noted that, in some alternative implementations, the functions noted in the block may occur out of the order noted in the figures. For example, two blocks shown in succession may, in fact, be executed substantially concurrently, or the blocks may sometimes be executed in the reverse order, depending upon the functionality involved. It will also be noted that each block of the block diagrams and/or flowchart illustration, and combinations of blocks in the block diagrams and/or flowchart illustration, can be implemented by special purpose hardware-based systems which perform the specified functions or acts, or combinations of special purpose hardware and computer instructions.
Finally, it should be noted that: the embodiments in the present description are described in a progressive manner, each embodiment focuses on differences from other embodiments, and the same and similar parts among the embodiments are referred to each other. The system or the device disclosed by the embodiment corresponds to the method disclosed by the embodiment, so that the description is simple, and the relevant points can be referred to the method part for description.
The above examples are only intended to illustrate the technical solution of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.
Claims (10)
1. An in-line filter membrane integrity testing apparatus for in-line filter membrane integrity testing in the production of radioactive pharmaceutical fluids, said in-line filter membrane integrity testing apparatus comprising:
the two port filters that connect, detachably set up on the production line of radioactive liquid medicine includes:
a first communication port configured to introduce a radioactive liquid medicine or a pressurized gas into the dual communication port filter;
the second communication port is communicated with the first communication port; and
an outlet configured to discharge the radioactive liquid medicine or the pressurized gas from the dual communication port filter,
the gas filter is connected with the second communication port through a communication pipe, and a switch valve is arranged on the communication pipe and is configured to be in a closed state when an online filter membrane integrity test is executed and to be in an open state when radiopharmaceutical filtration is executed; and
a first three-way valve and a second three-way valve which are respectively arranged at two sides of the dual-connection port filter, wherein the first end and the second end of the first three-way valve are respectively connected with the liquid inlet pipe and the first connection port of the dual-connection port filter, the third end of the first three-way valve is connected with the air inlet pipe, the first end and the second end of the second three-way valve are respectively connected with the outlet and the liquid outlet pipe of the dual-connection port filter, the third end of the second three-way valve is connected with the air outlet pipe,
the filter with two communicating ports comprises:
a first housing; and
a liquid filtering membrane disposed inside the first housing, dividing the first housing into a first cavity and a second cavity, the liquid filtering membrane configured to allow liquid to pass therethrough and remove bacteria in the liquid,
the first communicating port and the second communicating port are arranged on one side of the liquid filtering membrane and are communicated with the first cavity, and the outlet is arranged on the other side of the liquid filtering membrane and is communicated with the second cavity.
2. The in-line filter membrane integrity testing device of claim 1, wherein the first three-way valve is configured to switch between a first state and a second state, and the second three-way valve is configured to switch between a third state and a fourth state,
when the first three-way valve is in a first state and the second three-way valve is in a third state, the liquid inlet pipe, the dual-connection port filter and the liquid outlet pipe form a passage so that the radioactive liquid medicine flows through the passage to filter bacteria;
when first three-way valve is located the second state just when the second three-way valve is located the fourth state, the intake pipe intercommunication the first mouth of doubly-linked mouth filter the outlet duct intercommunication the export of doubly-linked mouth filter to realize online filter membrane integrality test.
3. The in-line filter membrane integrity testing device of claim 1 or 2, wherein the dual port filter further comprises:
the first connecting pipe extends from the first shell and is communicated with the first cavity, and the first communication port and the second communication port are arranged on the first connecting pipe; and
and the second connecting pipe extends from the first shell and is communicated with the second cavity, and the outlet is arranged on the second connecting pipe.
4. The in-line filter membrane integrity testing device of claim 3, wherein the first connection tube comprises:
the first sub-pipe extends from the first shell along the direction far away from the first cavity and is communicated with the first cavity, and the first communication port is arranged at the end part of the first sub-pipe far away from the first shell; and
and the second sub-pipe extends from the middle part of the first sub-pipe along the direction which is basically vertical to the first sub-pipe and is communicated with the first sub-pipe, and the second communication port is arranged at the end part of the second sub-pipe, which is far away from the first sub-pipe.
5. The in-line filter membrane integrity testing device of claim 1 or 2, wherein the dual port filter further comprises:
the third connecting pipe extends from the first shell and is communicated with the first cavity, and the first communication port is arranged on the third connecting pipe;
a fourth connecting pipe extending from the first housing and communicating with the first cavity, the second communicating port being provided on the fourth connecting pipe,
and
and the second connecting pipe extends from the first shell and is communicated with the second cavity, and the outlet is arranged on the second connecting pipe.
6. The in-line filter membrane integrity testing apparatus of claim 1 or 2, wherein the gas filter comprises:
a second housing;
and the gas filtering membrane is arranged in the second shell and divides the second shell into a third cavity and a fourth cavity, and the gas filtering membrane is configured to allow gas to pass and prevent liquid from passing.
7. The in-line filter membrane integrity testing apparatus of claim 1 or 2, wherein at least a portion of the in-line filter membrane integrity testing apparatus is disposed within a shielded isolation box.
8. An in-line filter membrane integrity test method using the in-line filter membrane integrity test apparatus of any one of claims 1 to 7, the in-line filter membrane integrity test method comprising:
switching the first three-way valve to a first state and the second three-way valve to a third state, opening the switch valve, allowing the pressurized liquid medicine to flow through the liquid inlet pipe, enter the double-connection-port filter through the first connection port, filter and discharge the liquid medicine through the liquid outlet pipe; and
and switching the first three-way valve to a second state and switching the second three-way valve to a fourth state, closing the switch valve, and allowing the test gas to enter the double-communication-port filter through the gas inlet pipe to perform an online filter membrane integrity test.
9. The in-line filter membrane integrity test method of claim 8, wherein prior to switching the first three-way valve to the second state and the second three-way valve to the fourth state, and closing the on-off valve, the in-line filter membrane integrity test method further comprises:
the filter with the double communication port is rinsed with water for injection to infiltrate the liquid filtration membrane in the filter with the double communication port.
10. Use of an in-line filtration membrane integrity test apparatus according to any one of claims 1 to 7 in an in-line filtration membrane integrity test.
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| JP2706853B2 (en) * | 1991-01-16 | 1998-01-28 | ハウス食品株式会社 | Membrane filter integrity inspection method and inspection device |
| WO2011072008A2 (en) * | 2009-12-10 | 2011-06-16 | Nephros, Inc. | Means for testing filter integrity in a liquid purification system |
| SG11201702936VA (en) * | 2014-12-31 | 2017-05-30 | Emd Millipore Corp | Interface module for filter integrity testing |
| US11156219B2 (en) * | 2015-11-10 | 2021-10-26 | Repligen Corporation | Disposable alternating tangential flow filtration units |
| EP3560577A1 (en) * | 2018-04-25 | 2019-10-30 | Gambro Lundia AB | Apparatus and method for testing integrity of an ultrafilter membrane |
| WO2019229872A1 (en) * | 2018-05-30 | 2019-12-05 | 旭化成メディカル株式会社 | Leak detection device and leak detection method |
| CN108744988B (en) * | 2018-08-15 | 2023-10-24 | 河南省药品医疗器械检验院(河南省疫苗批签中心) | Air filter/membrane liquid bacteria interception capability test module for transfusion |
| CN214749621U (en) * | 2020-12-24 | 2021-11-16 | 上海原子科兴药业有限公司 | Device for on-line detecting integrity of radioactive drug filter membrane |
| CN215196355U (en) * | 2021-03-15 | 2021-12-17 | 南京江原安迪科正电子研究发展有限公司 | Sterile filtration and filter membrane integrity test system |
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