A parallel two-stage sterilizing filter element online integrity detection process

Abstract

The present invention provides a parallel two-stage sterilizing filter element online integrity detection process, which belongs to the field of liquid preparation filter element detection technology. It solves the problems of low efficiency of online integrity detection of existing sterilizing filter elements, which leads to shutdown, and difficulty in replacing filter elements. The parallel two-stage sterilizing filter element online integrity detection process includes the following steps: step one, pure steam sterilization; step two, closed detection air circuit; step three, filter element cooling; step four, wetting treatment; step five, system isolation; step six, integrity detection; step seven, integrity detection again: step eight, filter element replacement; step nine, re-integrity detection; step ten, online integrity detection after use. The pipeline layout of the present invention is reasonable, and the integrity detection of the sterilizing filter can be efficiently performed; the parallel two-stage redundant sterilizing filter design avoids shutdown, and the filter element replacement equipment cooperates with the sterilizing filter to facilitate the rapid replacement of the filter element.

Description

Technical Field

[0001] The invention belongs to the technical field of liquid preparation filter element detection, and relates to an online integrity detection process for a parallel two-stage sterilizing filter element. Background Art

[0002] In the pharmaceutical industry, after the liquid preparation tank is configured and before filling, the liquid medicine will pass through the sterilization filter to make it sterile. This requires the filter element of the filter to be intact and undamaged during filtration. Therefore, integrity testing of the filter element after steam sterilization and filling is a necessary requirement of the filtration process to ensure the safety of the filtration process. Through integrity testing, the integrity of the filter itself and correct installation can be determined.

[0003] During the traditional online integrity test of the filter element, effective online sterilization cannot be performed, and the filter is directly connected to the integrity tester for testing. As a result, when the filter element needs to be sterilized and the integrity test is performed before use, the test gas directly enters the filter element to be tested through the integrity tester, and the sterility of the filter element cannot be guaranteed.

[0004] In addition, the existing integrity detection system generally only has a single filter. If the filter element is unqualified, replacement requires stopping production. After the integrity detection system is completed, the filter element needs to be replaced manually, which is inefficient.

[0005] Based on this, we proposed an online integrity detection process for parallel two-stage sterilizing filter elements. Summary of the invention

[0006] The purpose of the present invention is to address the above-mentioned problems existing in the existing technology and propose a parallel two-stage sterilizing filter element online integrity detection process. The technical problem to be solved by the invention is: how to achieve efficient integrity detection of the sterilizing filter through reasonable layout of pipelines; and adopt a parallel two-stage redundant sterilizing filter design to avoid production stoppage, and at the same time, the online filter element can be quickly replaced.

[0007] The purpose of the present invention can be achieved by the following technical solutions:

[0008] A parallel two-stage sterilizing filter element online integrity detection process comprises the following steps:

[0009] Step 1, pure steam sterilization: pure steam pipelines are used to sterilize all production pipelines and the primary sterilizing filter and the secondary sterilizing filter. The pressure sensor is used to detect the pressure difference before and after the filter element of the sterilizing filter, and the temperature sensor is used to detect the cold spot temperature in real time. When the readings of the two temperature sensors are >121°C, the sterilization is completed after 30 minutes. If the temperature drops during the process or the pressure difference before and after the sterilizing filter is greater than or equal to 0.5 bar, the timing is restarted.

[0010] Step 2: Close the detection gas circuit: Connect the integrity test machine bypass in series to the nitrogen compressed air pipeline of the CIP cleaning supply pipeline of the two sterilizing filters to form a closed detection gas circuit, and set a liquid level sensor on the top of each sterilizing filter to measure the water volume of the sterilizing filter;

[0011] Step 3, filter element cooling: After the CIP cleaning supply pipeline is sterilized in situ, sterile compressed air is injected through the air pipeline to cool the filter element of each sterilizing filter in the CIP cleaning supply pipeline until it cools to 23-27°C;

[0012] Step 4, wetting treatment: Take water from the water for injection point, and fill the primary sterilizing filter and the secondary sterilizing filter with water in turn through the connected pipes to wet them. When wetting, open the valve on the top of the filter. When water is observed flowing through the pipe sight glass, it proves that the inside of the filter housing has been filled with wetting water. Close the valve on the top of the filter, and observe the pressure sensor at the rear end of the filter. When the pressure value is close to the value of the pressure sensor at the front end of the filter, it means that the entire sterilizing filter has been wetted.

[0013] Step 5, system isolation: When the two-stage sterilizing filters are fully wetted, open the drain valves on the front and rear end pipes of the sterilizing filters to drain the inside of the filter housing. Since steam sterilization has been completed at this time, the entire pipeline system is in a sterile state. When draining, in order to prevent the sewage backflow in the sewage pipe from destroying the sterility of the system, an isolation tank is set up, and the water that wets the filter element is drained to the isolation tank. Through the principle of water seal in the isolation tank, the sterile system is isolated from the sewage system;

[0014] Step 6, integrity test: After the filter element is wetted, perform integrity test on the filter element. Connect the air pipe on the integrity tester to the integrity test port reserved in the filtration system, turn on the integrity tester with set parameters, and judge whether the filter element is damaged by the result of the integrity tester. If the test result is qualified, it means that the filter element is not damaged; if the test result is unqualified, proceed to step 7;

[0015] Step 7, integrity test again: if it fails, return to step 3 to step 5 and perform a second integrity test. If it still fails, it means that the filter element is scrapped and needs to be replaced. If it passes, but the test value is very close to or in a critical state with the standard judgment value, return to step 3 to step 5 and perform a third integrity test to re-judge whether it passes. If the third test value is still close to or in a critical state, the filter element needs to be replaced.

[0016] Step 8, filter element replacement: Move the filter element replacement device to the position of the filter element that needs to be replaced, unscrew the filter housing, remove the core, replace the core, lock the filter element and lock the filter housing for the sterilizing filter in turn. After completing the filter element replacement, move the filter element replacement device away, remove the filter element, clean it, reuse it or scrap it;

[0017] Step 9, re-test the integrity: If the integrity test fails, replace the new filter element and re-sterilize the single sterilizing filter and the single system with steam; close all valves in the system when replacing the filter element. After the replacement is completed, open the steam inlet valve of the filter to be sterilized and the condensate discharge valve. When the temperature detection probe on the condensate discharge pipeline shows that the temperature is above 121°C and maintained for 30 minutes, the sterilization is completed. After completion, introduce clean compressed air to replace the remaining steam in the system; after replacement, re-test the filter integrity according to steps 4 to 7;

[0018] Step 10: Perform online integrity check after use:

[0019] S1: The integrity test machine is bypassed and connected in series to the nitrogen compressed air pipeline of the CIP cleaning supply pipeline including at least one sterilizing filter to form a closed detection gas circuit, and a liquid level sensor is set on the top of each sterilizing filter to measure the water volume of the sterilizing filter;

[0020] S2: For water-based solutions, after the liquid is filtered, sterile air is directly introduced into the sterilizing filter to perform integrity testing through a bubble point test, diffusion flow test or pressure retention test. For organic solvent solutions, after the liquid is filtered, the filter element is removed through a filter element replacement device, cleaned, and then installed in the filter housing. The following steps are the same as for water-based solutions.

[0021] S3: If the test is qualified, it means that the filter element is intact and the sterilization and filtration of the drug can be effectively guaranteed by data: if it is unqualified, return to execute S2 once; if it is still unqualified, it means that the filter element is damaged and needs to be replaced by the filter element replacement equipment; in addition, the batch of drugs produced must be sampled and tested or scrapped as a whole; if it is qualified, but the test value and the standard judgment value are very close to or in a critical state, then the batch of drugs is qualified but the filter element is not recommended to be used next time and needs to be replaced by the filter element replacement equipment.

[0022] The online integrity detection process of the parallel two-stage sterilizing filter element also includes an injection water pipeline, a pure steam pipeline, a nitrogen compressed air pipeline, a CIP cleaning supply pipeline, a condensate discharge pipeline, a CIP cleaning discharge pipeline, a wastewater discharge pipeline, a material conveying pipeline, a material circulation pipeline, an integrity testing machine and an isolation tank; the material circulation pipeline is connected to the material conveying pipeline, and three sterilizing filters are arranged on the material conveying pipeline. The material circulation pipeline is connected between the first two sterilizing filters, and the connection point is connected to the CIP cleaning discharge pipeline, and the last two sterilizing filters are connected to the integrity testing machine, and the connecting pipeline A T-type filter is provided on it, the first filter is connected to the pure steam pipeline, the isolation tank is connected to the material circulation pipeline, and the connecting pipeline is connected to the condensate discharge pipeline, and the connection points are located on both sides of the last two sterilizing filters, and a heating filter is provided on the isolation tank; the three sterilizing filters are all connected to the injection water pipeline, the pure steam pipeline, the nitrogen compressed air pipeline, the CIP cleaning supply pipeline, and the condensate discharge pipeline; water receiving trays are provided under the three sterilizing filters, and the water receiving trays and the isolation tanks are connected to the wastewater discharge pipeline; pipeline mirrors are provided on the three sterilizing filters, and the pipeline mirrors are connected to the condensate discharge pipeline.

[0023] The injection water pipeline, pure steam pipeline, nitrogen compressed air pipeline, CIP cleaning supply pipeline, condensate discharge pipeline, CIP cleaning discharge pipeline, wastewater discharge pipeline, material conveying pipeline, and material circulation pipeline are all inclined pipelines with the feed end higher than the discharge end.

[0024] The sterilizing filter in step one includes a diverter base, a filter housing and a filter element. A sealing ring is provided on the outer side of the upper end surface of the diverter base. A sealing gasket, a screw-on groove and a plurality of screw-on protrusions evenly distributed around the circumference are provided on the upper end surface of the diverter base and the lower end surface of the filter housing. A sealing groove is provided on the outer side of the lower end surface of the filter housing. When the diverter base and the filter housing are screwed together, the sealing ring is inserted into the sealing groove, and the screw-on protrusions are screwed into the corresponding screw-on grooves respectively. The two sealing gaskets are in contact with each other. An exhaust channel and a filter element snap-on hole are provided on the upper end of the diverter base. The filter element can be detachably screwed into the filter element snap-on hole. A pressure sensor and a temperature sensor are provided on the filter housing.

[0025] With the above structure, the filter element is screwed into the filter element engagement hole. When the diverter base and the filter housing are screwed together, the sealing ring is inserted into the sealing groove. The screw-in engagement protrusions are respectively screwed into the corresponding screw-in engagement grooves. The two sealing gaskets are in contact with each other. The exhaust channel is used to exhaust air. The filter element engagement hole and the filter element cooperate to filter water. The pressure sensor is used to detect the pressure difference before and after the filter element of the sterilizing filter. The temperature sensor is used to detect the cold spot temperature in real time. When the readings of the two temperature sensors are >121°C.

[0026] The filter element replacement equipment in step eight includes a hand-pushed mobile cart, which is provided with a filter housing disassembly and assembly mechanism, a filter element switching mechanism and a rotating placement mechanism from left to right.

[0027] With the above structure, the hand-pushed mobile trolley is convenient for moving the device. The filter shell disassembly and assembly mechanism rotates the filter shell on the diversion base to disassemble and move it out. Then the filter element switching mechanism removes the filter element from the inside of the filter element engaging hole, and then the new filter element is taken out from the rotating placement mechanism and screwed into the inside of the filter element engaging hole. The filter shell disassembly and assembly mechanism assembles the filter shell to the diversion base again, and the rotating placement mechanism rotates the angle so that the position where the filter element is installed is opposite to the sterilizing filter.

[0028] The hand-pushed mobile trolley comprises a vehicle body, a placing box is fixed on the upper end of the vehicle body, a hand push rod is fixed on the placing box, an electric lifting rod is rotatably provided on the upper end of the vehicle body, a top plate is fixed on the upper end of the electric lifting rod, and an avoidance gap is opened on the top plate.

[0029] With the above structure, the user grasps the push rod to push the device to move, rotates the electric lifting rod, and the top plate is located on the outside of the vehicle body, so that the avoidance gap of the device can be moved to the sterilization filter to replace the filter element.

[0030] The filter housing disassembly and assembly mechanism includes a transverse screw rod member, which is fixed at the lower end of the top plate and is located on one side of the avoidance gap. A mounting frame plate is provided on the transverse screw rod member, a rotating motor is fixed at the upper end of the mounting frame plate, an arc gear is slidably provided at the lower end of the mounting frame plate, a driving gear is fixed on the output shaft of the rotating motor, the driving gear is meshed with the arc gear, a fixed base plate is fixed at the lower end of the fixed base plate, a clamping cylinder is fixed at the lower end of the fixed base plate, and two symmetrically arranged rotating clamping claws are provided on the clamping cylinder.

[0031] With the above structure, the transverse screw rod drives the mounting frame to move horizontally left and right, the output shaft of the rotating motor drives the driving gear to rotate, the driving gear meshes with the arc gear, drives the arc gear to perform circular rotation and sliding at the lower end of the mounting frame, drives the fixed base plate to rotate, drives the clamping cylinder to rotate, the clamping cylinder drives two symmetrically arranged screwing claws to move relative to each other, clamps the filter shell, drives the filter shell to rotate, and removes the filter shell.

[0032] The filter element switching mechanism includes a fixed frame, which is fixed to the lower end of the top plate and is located on the other side of the avoidance gap. A lifting cylinder is fixed on the fixed frame, and a sliding base is fixed to the telescopic end of the lifting cylinder, and a rotating motor is fixed to the sliding base. Two sliding plates symmetrically arranged are fixed on the output shaft of the rotating motor, and electric push plates are fixed at the ends of the sliding plates. A rotation motor is fixed at the upper end of the electric push plate, and a rotation gear is slidably provided at the lower end of the electric push plate. A rotating gear is fixed on the output shaft of the rotation motor, and the rotating gear is meshed with the rotation gear. A rotation bottom plate is fixed to the lower end of the rotation bottom plate, and a rotation cylinder is fixed to the lower end of the rotation bottom plate, and two symmetrically arranged rotation claws are provided on the rotation cylinder.

[0033] By adopting the above structure, the two electric push plates are pushed out, and the two rotary clamps on both sides are respectively clamped on the unqualified filter element on the shunt base and the new filter element on the rotary placement mechanism, and the output shaft of the rotary motor drives the rotary gear to rotate, and the rotary gear is meshed with the rotary gear, driving the rotary gear to perform circular arc rotation and sliding at the lower end of the electric push plate, driving the rotary base plate to rotate, driving the rotary cylinder to rotate, and the rotary cylinder drives the two symmetrically arranged rotary clamps to move relative to each other, clamp the filter shell, and drive the filter element to rotate. At the same time, the telescopic end of the lifting cylinder drives the sliding base to rise, and the filter element is removed from the filter element engaging hole of the shunt base. At the same time, the rotary clamps on the other side remove the filter element from the rotary placement mechanism, and then the output shaft of the rotating motor drives the two sliding plates symmetrically arranged at the center to rotate, and the output shaft of the rotary motor on the side equipped with the new filter element rotates in the opposite direction, and the telescopic end of the lifting cylinder drives the sliding base to descend, and the new filter element is screwed into the inside of the filter element engaging hole, and the unqualified filter element is placed on the rotary placement mechanism.

[0034] The rotating placement mechanism includes an indexing motor, which is fixed at the lower end of the top plate and located on the side of the fixed frame. A clamping base is fixed on the output shaft of the indexing motor, and a plurality of circumferentially evenly distributed engaging seats are fixed on the clamping base. Two symmetrically arranged claws are rotatably provided on the engaging seat, and a tension spring is provided between the end of the claw and the engaging seat.

[0035] With the above structure, the filter element is inserted into two symmetrically arranged claws, and the tension spring is stressed so that the two symmetrically arranged claws clamp the filter element. The output shaft of the indexing motor drives the clamping base to rotate, and each rotation is 360° divided by the quotient of the number of engaging seats, thereby ensuring stable removal of the new filter element and insertion of the unqualified filter element.

[0036] Compared with the prior art, this parallel two-stage sterilizing filter element online integrity detection process has the following advantages:

[0037] Through the cooperation of injection water pipeline, pure steam pipeline, nitrogen compressed air pipeline, CIP cleaning supply pipeline, condensate discharge pipeline, CIP cleaning discharge pipeline, wastewater discharge pipeline, material conveying pipeline, material circulation pipeline, integrity testing machine and isolation tank, the layout of each pipeline is reasonable, which can efficiently perform integrity testing on the sterilizing filter to ensure the sterility of the finished product;

[0038] The parallel two-stage redundant sterilizing filter design is adopted. If the filter element of one sterilizing filtration system is blocked during use, it can be switched to the other sterilizing filtration system in time to continue production, avoiding production suspension due to filter element blockage and a series of pre-filtration preparation work;

[0039] The sterilizing filter is matched with the diverter base, the filter housing and the filter element. The diverter base, the filter housing and the diverter base and the filter element can be quickly twisted and disassembled, so that the filter element can be quickly replaced.

[0040] The filter element replacement equipment can quickly and automatically replace the filter element of the sterilizing filter, reducing the replacement time of the filter element and meeting the needs of liquid preparation. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] Figure 1 It is a process diagram of the online integrity detection of the filter of the present invention.

[0042] Figure 2 It is the left half process diagram of the filter online integrity detection of the present invention.

[0043] Figure 3 It is the right half process diagram of the filter online integrity detection of the present invention.

[0044] Figure 4 It is a three-dimensional structural schematic diagram of the filter element replacement device in the present invention.

[0045] Figure 5 It is a front view structural schematic diagram of the filter element replacement device in the present invention.

[0046] Figure 6 It is a structural schematic diagram of the hand-pushed mobile trolley in the present invention.

[0047] Figure 7 It is a schematic diagram of the structure of the sterilizing filter in the present invention.

[0048] Figure 8 It is a structural schematic diagram of the filter housing disassembly and assembly mechanism in the present invention.

[0049] Fig. 9 It is a structural schematic diagram of the filter element switching mechanism in the present invention.

[0050] Fig.10 It is a structural schematic diagram of the rotating placement mechanism in the present invention.

[0051] In the figure, 1, sterilizing filter; 2, hand-pushed mobile trolley; 3, filter housing disassembly and assembly mechanism; 4, rotating placement mechanism; 5, filter element switching mechanism; 6, vehicle body; 7, electric lifting rod; 8, top plate; 9, avoidance gap; 10, hand push rod; 11, placement box; 12, filter housing; 13, filter element; 14, diversion base; 15, exhaust channel; 16, filter element engaging hole; 17, sealing ring; 18, screw-on convex; 19, sealing gasket; 20, transverse screw rod; 21. Mounting frame; 22. Rotating motor; 23. Arc gear; 24. Screwing clamp; 25. Clamping cylinder; 26. Fixed base plate; 27. Fixed frame; 28. Lifting cylinder; 29. ​​Sliding base; 30. Rotating motor; 31. Sliding plate; 32. Electric push plate; 33. Rotating cylinder; 34. Rotating base plate; 35. Rotating gear; 36. Rotating motor; 37. Transposition motor; 38. Clamping base; 39. Engaging seat; 40. Clamping claw. DETAILED DESCRIPTION

[0052] The following are specific embodiments of the present invention and the accompanying drawings to further describe the technical solution of the present invention, but the present invention is not limited to these embodiments.

[0053] like Figure 1-Figure 10 As shown, the online integrity detection process of the parallel two-stage sterilizing filter element includes the following steps:

[0054] Step 1, pure steam sterilization: pure steam pipelines are used to sterilize all production pipelines and the primary sterilizing filter and the secondary sterilizing filter. The pressure sensor is used to detect the pressure difference before and after the filter element of the sterilizing filter, and the temperature sensor is used to detect the cold spot temperature in real time. When the readings of the two temperature sensors are >121°C, the sterilization is completed after 30 minutes. If the temperature drops during the process or the pressure difference before and after the sterilizing filter is greater than or equal to 0.5 bar, the timing is restarted.

[0055] Step 2: Close the detection gas circuit: Connect the integrity test machine bypass in series to the nitrogen compressed air pipeline of the CIP cleaning supply pipeline of the two sterilizing filters to form a closed detection gas circuit, and set a liquid level sensor on the top of each sterilizing filter to measure the water volume of the sterilizing filter;

[0056] Step 3, filter element cooling: After the CIP cleaning supply pipeline is sterilized in situ, sterile compressed air is injected through the air pipeline to cool the filter element of each sterilizing filter in the CIP cleaning supply pipeline until it cools to 23-27°C;

[0057] Step 4, wetting treatment: Take water from the water for injection point, and fill the primary sterilizing filter and the secondary sterilizing filter with water in turn through the connected pipes to wet them. When wetting, open the valve on the top of the filter. When water is observed flowing through the pipe sight glass, it proves that the inside of the filter housing has been filled with wetting water. Close the valve on the top of the filter, and observe the pressure sensor at the rear end of the filter. When the pressure value is close to the value of the pressure sensor at the front end of the filter, it means that the entire sterilizing filter has been wetted.

[0058] Step 5, system isolation: When the two-stage sterilizing filters are fully wetted, open the drain valves on the front and rear end pipes of the sterilizing filters to drain the inside of the filter housing. Since steam sterilization has been completed at this time, the entire pipeline system is in a sterile state. When draining, in order to prevent the sewage backflow in the sewage pipe from destroying the sterility of the system, an isolation tank is set up, and the water that wets the filter element is drained to the isolation tank. Through the principle of water seal in the isolation tank, the sterile system is isolated from the sewage system;

[0059] Step 6, integrity test: After the filter element is wetted, perform integrity test on the filter element. Connect the air pipe on the integrity tester to the integrity test port reserved in the filtration system, turn on the integrity tester with set parameters, and judge whether the filter element is damaged by the result of the integrity tester. If the test result is qualified, it means that the filter element is not damaged; if the test result is unqualified, proceed to step 7;

[0060] Step 7, integrity test again: if it fails, return to step 3 to step 5 and perform a second integrity test. If it still fails, it means that the filter element is scrapped and needs to be replaced. If it passes, but the test value is very close to or in a critical state with the standard judgment value, return to step 3 to step 5 and perform a third integrity test to re-judge whether it passes. If the third test value is still close to or in a critical state, the filter element needs to be replaced.

[0061] Step 8, filter element replacement: Move the filter element replacement device to the position of the filter element that needs to be replaced, unscrew the filter housing, remove the core, replace the core, lock the filter element and lock the filter housing for the sterilizing filter in turn. After completing the filter element replacement, move the filter element replacement device away, remove the filter element, clean it, reuse it or scrap it;

[0062] Step 9, re-test the integrity: If the integrity test fails, replace the new filter element and re-sterilize the single sterilizing filter and the single system with steam; close all valves in the system when replacing the filter element. After the replacement is completed, open the steam inlet valve of the filter to be sterilized and the condensate discharge valve. When the temperature detection probe on the condensate discharge pipeline shows that the temperature is above 121°C and maintained for 30 minutes, the sterilization is completed. After completion, introduce clean compressed air to replace the remaining steam in the system; after replacement, re-test the filter integrity according to steps 4 to 7;

[0063] Step 10: Perform online integrity check after use:

[0064] S1: The integrity test machine is bypassed and connected in series to the nitrogen compressed air pipeline of the CIP cleaning supply pipeline including at least one sterilizing filter to form a closed detection gas circuit, and a liquid level sensor is set on the top of each sterilizing filter to measure the water volume of the sterilizing filter;

[0065] S2: For water-based solutions, after the liquid is filtered, sterile air is directly introduced into the sterilizing filter to perform integrity testing through a bubble point test, diffusion flow test or pressure retention test. For organic solvent solutions, after the liquid is filtered, the filter element is removed through a filter element replacement device, cleaned, and then installed in the filter housing. The following steps are the same as for water-based solutions.

[0066] S3: If the test is qualified, it means that the filter element is intact and the sterilization and filtration of the drug can be effectively guaranteed by data: if it is unqualified, return to execute S2 once; if it is still unqualified, it means that the filter element is damaged and needs to be replaced by the filter element replacement equipment; in addition, the batch of drugs produced must be sampled and tested or scrapped as a whole; if it is qualified, but the test value and the standard judgment value are very close to or in a critical state, then the batch of drugs is qualified but the filter element is not recommended to be used next time and needs to be replaced by the filter element replacement equipment.

[0067] The online integrity detection process of the parallel two-stage sterilizing filter element also includes an injection water pipeline, a pure steam pipeline, a nitrogen compressed air pipeline, a CIP cleaning supply pipeline, a condensate discharge pipeline, a CIP cleaning discharge pipeline, a wastewater discharge pipeline, a material conveying pipeline, a material circulation pipeline, an integrity testing machine and an isolation tank; the material circulation pipeline is connected to the material conveying pipeline, and three sterilizing filters 1 are arranged on the material conveying pipeline. The material circulation pipeline is connected between the first two sterilizing filters 1, and the connection point is connected to the CIP cleaning discharge pipeline, and the last two sterilizing filters 1 are connected to the integrity testing machine, and the connection pipeline A T-type filter is provided, the first filter is connected to the pure steam pipeline, the isolation tank is connected to the material circulation pipeline, and the connecting pipeline is connected to the condensate discharge pipeline, and the connection points are located on both sides of the last two sterilizing filters 1, and a heating filter is provided on the isolation tank; the three sterilizing filters 1 are all connected to the injection water pipeline, the pure steam pipeline, the nitrogen compressed air pipeline, the CIP cleaning supply pipeline, and the condensate discharge pipeline; a water receiving tray is provided under the three sterilizing filters 1, and the water receiving tray and the isolation tank are connected to the wastewater discharge pipeline; the three sterilizing filters 1 are provided with a pipeline test mirror, and the pipeline test mirror is connected to the condensate discharge pipeline.

[0068] Injection water pipelines, pure steam pipelines, nitrogen compressed air pipelines, CIP cleaning supply pipelines, condensate discharge pipelines, CIP cleaning discharge pipelines, wastewater discharge pipelines, material conveying pipelines, and material circulation pipelines are all inclined pipelines with the feed end higher than the discharge end.

[0069] The sterilizing filter 1 in step one includes a diverter base 14, a filter housing 12 and a filter element 13. A sealing ring 17 is provided on the outer side of the upper end surface of the diverter base 14. A sealing gasket 19, a screw-on groove and a plurality of screw-on protrusions 18 evenly distributed around the circumference are provided on the upper end surface of the diverter base 14 and the lower end surface of the filter housing 12. A sealing groove is provided on the outer side of the lower end surface of the filter housing 12. When the diverter base 14 and the filter housing 12 are screwed together, the sealing ring 17 is inserted into the sealing groove, and the screw-on protrusions 18 are screwed into the corresponding screw-on grooves respectively. The two sealing gaskets 19 are in contact with each other. An exhaust channel 15 and a filter element snap-on hole 16 are provided on the upper end of the diverter base 14. The filter element 13 is detachably screwed into the filter element snap-on hole 16. A pressure sensor and a temperature sensor are provided on the filter housing 12.

[0070] The filter element 13 is screwed into the filter element engaging hole 16. When the diverter base 14 and the filter housing 12 are screwed together, the sealing ring 17 is inserted into the sealing groove. The screw-in engaging protrusions 18 are respectively screwed into the corresponding screw-in grooves. The two sealing gaskets 19 are in contact with each other. The exhaust channel 15 is used to exhaust air. The filter element engaging hole 16 and the filter element 13 cooperate to filter water. The pressure sensor is used to detect the pressure difference before and after the filter element 13 of the sterilizing filter 1. The temperature sensor is used to detect the cold spot temperature in real time. When the readings of the two temperature sensors are >121°C.

[0071] The filter element replacement equipment in step eight includes a hand-pushed mobile cart 2, which is provided with a filter housing disassembly and assembly mechanism 3, a filter element switching mechanism 5 and a rotating placement mechanism 4 from left to right.

[0072] The hand-pushed mobile trolley 2 is convenient for moving the device. The filter housing disassembly and assembly mechanism 3 rotates and disassembles the filter housing 12 on the diverter base 14 and moves it out. Then the filter element switching mechanism 5 removes the filter element 13 from the inside of the filter element engaging hole 16, and then the new filter element 13 is removed from the rotating placement mechanism 4 and screwed into the inside of the filter element engaging hole 16. The filter housing disassembly and assembly mechanism 3 assembles the filter housing 12 onto the diverter base 14 again, and the rotating placement mechanism 4 rotates the angle so that the position where the filter element 13 is installed is opposite to the sterilizing filter 1.

[0073] The hand-pushed mobile trolley 2 includes a body 6, a storage box 11 is fixed on the upper end of the body 6, a hand push rod 10 is fixed on the storage box 11, an electric lifting rod 7 is rotatably provided on the upper end of the body 6, a top plate 8 is fixed on the upper end of the electric lifting rod 7, and an avoidance gap 9 is opened on the top plate 8.

[0074] The user holds the push rod 10 to push the device to move, rotates the electric lifting rod 7 180 degrees, and the top plate 8 is located outside the vehicle body 6, so that the avoidance gap 9 of the device can be moved to the sterilizing filter 1 to replace the filter element 13.

[0075] The filter housing disassembly and assembly mechanism 3 includes a transverse screw rod member 20, which is fixed at the lower end of the top plate 8 and is located on one side of the avoidance gap 9. A mounting frame plate 21 is provided on the transverse screw rod member 20, a rotating motor 22 is fixed to the upper end of the mounting frame plate 21, and an arc gear 23 is slidably provided at the lower end of the mounting frame plate 21. A driving gear is fixed to the output shaft of the rotating motor 22, and the driving gear is meshed with the arc gear 23. A fixed base plate 26 is fixed to the lower end of the arc gear 23, and a clamping cylinder 25 is fixed to the lower end of the fixed base plate 26. The clamping cylinder 25 is provided with two symmetrically arranged screwing jaws 24.

[0076] The transverse screw rod 20 drives the mounting frame plate 21 to move horizontally left and right, and the output shaft of the rotating motor 22 drives the driving gear to rotate. The driving gear is engaged with the arc gear 23, driving the arc gear 23 to perform circular rotation and sliding at the lower end of the mounting frame plate 21, driving the fixed base plate 26 to rotate, driving the clamping cylinder 25 to rotate, and the clamping cylinder 25 drives two symmetrically arranged screwing claws 24 to move relative to each other, clamping the filter housing 12, driving the filter housing 12 to rotate, and removing the filter housing 12.

[0077] The filter element switching mechanism 5 includes a fixed frame 27, which is fixed at the lower end of the top plate 8, and the fixed frame 27 is located on the other side of the avoidance gap 9. A lifting cylinder 28 is fixed on the fixed frame 27, and a sliding base 29 is fixed to the telescopic end of the lifting cylinder 28. A rotating motor 30 is fixed to the sliding base 29. Two sliding plates 31 symmetrically arranged at the center are fixed to the output shaft of the rotating motor 30. Electric push plates 32 are fixed to the ends of the sliding plates 31. A rotation motor 36 is fixed to the upper end of the electric push plate 32. A rotation gear 35 is slidably provided at the lower end of the electric push plate 32. A rotating gear is fixed to the output shaft of the rotation motor 36. The rotating gear is meshed with the rotation gear 35. A rotation bottom plate 34 is fixed to the lower end of the rotation bottom plate 34. A rotation cylinder 33 is fixed to the lower end of the rotation bottom plate 34. Two symmetrically arranged rotation claws are provided on the rotation cylinder 33.

[0078] The two electric push plates 32 are pushed out to clamp the two rotational clamps on both sides respectively on the unqualified filter element 13 on the diversion base 14 and the new filter element 13 on the rotation placement mechanism 4. The output shaft of the rotation motor 36 drives the rotation gear to rotate, and the rotation gear is engaged with the rotation gear 35, driving the rotation gear 35 to perform circular arc rotation and sliding at the lower end of the electric push plate 32, driving the rotation base plate 34 to rotate, driving the rotation cylinder 33 to rotate, and the rotation cylinder 33 drives the two symmetrically arranged rotational clamps to move relative to each other, clamping the filter housing 12, driving the filter element 13 to rotate, and at the same time, the lifting The telescopic end of the lowering cylinder 28 drives the sliding base 29 to rise, and the filter element 13 is removed from the filter element engaging hole 16 of the diverter base 14. At the same time, the rotary clamp on the other side removes the filter element 13 from the rotating placement mechanism 4. Then the output shaft of the rotating motor 30 drives the two centrally symmetrically arranged sliding plates 31 to rotate 180 degrees. The output shaft of the rotary motor 36 on the side with the new filter element 13 rotates in the opposite direction. The telescopic end of the lifting cylinder 28 drives the sliding base 29 to descend, and the new filter element 13 is screwed into the filter element engaging hole 16. The unqualified filter element 13 is placed on the rotating placement mechanism 4.

[0079] The rotating placement mechanism 4 includes an indexing motor 37, which is fixed at the lower end of the top plate 8 and is located on the side of the fixed frame 27. A clamping base 38 is fixed on the output shaft of the indexing motor 37, and a plurality of circumferentially evenly distributed engaging seats 39 are fixed on the clamping base 38. Two symmetrically arranged claws 40 are rotatably provided on the engaging seat 39, and a tension spring is provided between the end of the claw 40 and the engaging seat 39.

[0080] The filter element 13 is inserted into two symmetrically arranged claws 40, and the tension spring is stressed so that the two symmetrically arranged claws 40 clamp the filter element 13. The output shaft of the indexing motor 37 drives the clamping base 38 to rotate, and each rotation is 360° divided by the quotient of the number of engaging seats 39, ensuring the stable removal of the new filter element 13 and the insertion of the unqualified filter element 13.

[0081] Working principle of the filter element replacement device: the user grasps the push rod 10 to push the device to move, rotates the electric lifting rod 7 180 degrees, and the top plate 8 is located outside the vehicle body 6, so that the avoidance gap 9 of the device can be moved to the sterilizing filter 1 to replace the filter element 13;

[0082] The transverse screw rod 20 drives the mounting frame 21 to move horizontally left and right, and the output shaft of the rotating motor 22 drives the driving gear to rotate. The driving gear meshes with the arc gear 23, driving the arc gear 23 to perform circular rotation and sliding at the lower end of the mounting frame 21, driving the fixed base plate 26 to rotate, driving the clamping cylinder 25 to rotate, and the clamping cylinder 25 drives two symmetrically arranged screwing claws 24 to move relative to each other, clamping the filter housing 12, driving the filter housing 12 to rotate, and the filter housing 12 is removed and moved out.

[0083] The two electric push plates 32 are pushed out to clamp the two rotational clamps on both sides respectively on the unqualified filter element 13 on the diversion base 14 and the new filter element 13 on the rotation placement mechanism 4. The output shaft of the rotation motor 36 drives the rotation gear to rotate, and the rotation gear is engaged with the rotation gear 35, driving the rotation gear 35 to perform circular arc rotation and sliding at the lower end of the electric push plate 32, driving the rotation base plate 34 to rotate, driving the rotation cylinder 33 to rotate, and the rotation cylinder 33 drives the two symmetrically arranged rotational clamps to move relative to each other, clamping the filter housing 12, driving the filter element 13 to rotate, and at the same time, the lifting The telescopic end of the lowering cylinder 28 drives the sliding base 29 to rise, and the filter element 13 is removed from the filter element engaging hole 16 of the diverter base 14. At the same time, the rotary clamp on the other side removes the filter element 13 from the rotary placement mechanism 4. Then the output shaft of the rotating motor 30 drives the two centrally symmetrically arranged sliding plates 31 to rotate 180 degrees. The output shaft of the rotary motor 36 on the side with the new filter element 13 rotates in the opposite direction. The telescopic end of the lifting cylinder 28 drives the sliding base 29 to descend, and the new filter element 13 is screwed into the filter element engaging hole 16. The unqualified filter element 13 is placed on the rotary placement mechanism 4.

[0084] The filter element 13 is inserted into two symmetrically arranged claws 40, and the tension spring is stressed so that the two symmetrically arranged claws 40 clamp the filter element 13. The output shaft of the indexing motor 37 drives the clamping base 38 to rotate, and each rotation is 360° divided by the quotient of the number of engaging seats 39, ensuring the stable removal of the new filter element 13 and the insertion of the unqualified filter element 13.

[0085] In summary, through the cooperation of water for injection pipeline, pure steam pipeline, nitrogen compressed air pipeline, CIP cleaning supply pipeline, condensate discharge pipeline, CIP cleaning discharge pipeline, wastewater discharge pipeline, material conveying pipeline, material circulation pipeline, integrity testing machine and isolation tank, the layout of each pipeline is reasonable, and the integrity of the sterilizing filter 1 can be efficiently tested to ensure the sterility of the finished product;

[0086] The parallel two-stage redundant sterilizing filter design is adopted. If the filter element of one sterilizing filtration system is blocked during use, it can be switched to the other sterilizing filtration system in time to continue production, avoiding production suspension due to filter element blockage and a series of pre-filtration preparation work;

[0087] The sterilizing filter 1 cooperates with the flow diversion base 14, the filter housing 12 and the filter element 13, and the flow diversion base 14, the filter housing 12 and the flow diversion base 14 and the filter element 13 can be quickly twisted to disassemble and assemble, so as to facilitate the rapid replacement of the filter element 13;

[0088] The filter element 13 of the sterilizing filter 1 can be quickly and automatically replaced by the filter element replacement device, thereby reducing the replacement time of the filter element and meeting the requirements of liquid preparation.

[0089] The specific embodiments described herein are merely examples of the spirit of the present invention. Those skilled in the art may make various modifications or additions to the specific embodiments described or replace them in similar ways, but they will not deviate from the spirit of the present invention or exceed the scope defined by the appended claims.

Claims

1. A parallel two-stage sterilizing filter element online integrity detection process, characterized in that: The following steps are involved: Step 1, pure steam sterilization: pure steam pipelines are used to sterilize all production pipelines and the primary sterilizing filter and the secondary sterilizing filter. The pressure sensor is used to detect the pressure difference before and after the filter element of the sterilizing filter, and the temperature sensor is used to detect the cold spot temperature in real time. When the readings of the two temperature sensors are >121°C, the sterilization is completed after 30 minutes. If the temperature drops during the process or the pressure difference before and after the sterilizing filter is greater than or equal to 0.5 bar, the timing is restarted. Step 2: Close the detection gas circuit: Connect the integrity test machine bypass in series to the nitrogen compressed air pipeline of the CIP cleaning supply pipeline of the two sterilizing filters to form a closed detection gas circuit, and set a liquid level sensor on the top of each sterilizing filter to measure the water volume of the sterilizing filter; Step 3, filter element cooling: After the CIP cleaning supply pipeline is sterilized in situ, sterile compressed air is injected through the air pipeline to cool the filter element of each sterilizing filter in the CIP cleaning supply pipeline until it cools to 23-27°C; Step 4, wetting treatment: Take water from the water for injection point, and fill the primary sterilizing filter and the secondary sterilizing filter with water in turn through the connected pipes to wet them. When wetting, open the valve on the top of the filter. When water is observed flowing through the pipe sight glass, it proves that the inside of the filter housing has been filled with wetting water. Close the valve on the top of the filter, and observe the pressure sensor at the rear end of the filter. When the pressure value is close to the value of the pressure sensor at the front end of the filter, it means that the entire sterilizing filter has been wetted. Step 5, system isolation: When the two-stage sterilizing filters are fully wetted, open the drain valves on the front and rear end pipes of the sterilizing filters to drain the inside of the filter housing. Since steam sterilization has been completed at this time, the entire pipeline system is in a sterile state. When draining, in order to prevent the sewage backflow in the sewage pipe from destroying the sterility of the system, an isolation tank is set up, and the water that wets the filter element is drained to the isolation tank. Through the principle of water seal in the isolation tank, the sterile system is isolated from the sewage system; Step 6, integrity test: After the filter element is wetted, perform integrity test on the filter element. Connect the air pipe on the integrity tester to the integrity test port reserved in the filtration system, turn on the integrity tester with set parameters, and judge whether the filter element is damaged by the result of the integrity tester. If the test result is qualified, it means that the filter element is not damaged; if the test result is unqualified, proceed to step 7; Step 7, integrity test again: if it fails, return to step 3 to step 5 and perform a second integrity test. If it still fails, it means that the filter element is scrapped and needs to be replaced. If it passes, but the test value is very close to or in a critical state with the standard judgment value, return to step 3 to step 5 and perform a third integrity test to re-judge whether it passes. If the third test value is still close to or in a critical state, the filter element needs to be replaced. Step 8, filter element replacement: Move the filter element replacement device to the position of the filter element that needs to be replaced, unscrew the filter housing, remove the core, replace the core, lock the filter element and lock the filter housing for the sterilizing filter in turn. After completing the filter element replacement, move the filter element replacement device away, remove the filter element, clean it, reuse it or scrap it; Step 9, re-test the integrity: If the integrity test fails, replace the new filter element and re-sterilize the single sterilizing filter and the single system with steam; close all valves in the system when replacing the filter element. After the replacement is completed, open the steam inlet valve of the filter to be sterilized and the condensate discharge valve. When the temperature detection probe on the condensate discharge pipeline shows that the temperature is above 121°C and maintained for 30 minutes, the sterilization is completed. After completion, introduce clean compressed air to replace the remaining steam in the system; after replacement, re-test the filter integrity according to steps 4 to 7; Step 10: Perform online integrity test after use: S1: The integrity test machine is bypassed and connected in series to the nitrogen compressed air pipeline of the CIP cleaning supply pipeline including at least one sterilizing filter to form a closed detection gas circuit, and a liquid level sensor is set on the top of each sterilizing filter to measure the water volume of the sterilizing filter; S2: For water-based solutions, after the liquid is filtered, sterile air is directly introduced into the sterilizing filter to perform integrity testing through a bubble point test, diffusion flow test or pressure retention test. For organic solvent solutions, after the liquid is filtered, the filter element is removed through a filter element replacement device, cleaned, and then installed in the filter housing. The following steps are the same as for water-based solutions. S3: If the test is qualified, it means that the filter element is intact and the sterilization and filtration of the medicine can be effectively guaranteed by data. If it is unqualified, return to execute S2 once. If it is still unqualified, it means that the filter element is damaged and needs to be replaced by the filter element replacement equipment. In addition, the batch of medicines produced must be sampled and tested or scrapped as a whole. If it is qualified, but the test value and the standard judgment value are very close or in a critical state, then the batch of medicines is qualified but the filter element is not recommended to be used next time and needs to be replaced by the filter element replacement equipment. It also includes an injection water pipeline, a pure steam pipeline, a nitrogen compressed air pipeline, a CIP cleaning supply pipeline, a condensate discharge pipeline, a CIP cleaning discharge pipeline, a wastewater discharge pipeline, a material conveying pipeline, a material circulation pipeline, an integrity tester and an isolation tank; the material circulation pipeline is connected to the material conveying pipeline, three sterilizing filters (1) are arranged on the material conveying pipeline, the material circulation pipeline is connected between the first two sterilizing filters (1), and the connection point is connected to the CIP cleaning discharge pipeline, the last two sterilizing filters (1) are connected to the integrity tester, and a T-type filter is arranged on the connecting pipeline, the first filter The device is connected to the pure steam pipeline, the isolation tank is connected to the material circulation pipeline, and the connecting pipeline is connected to the condensate discharge pipeline, and the connection points are located on both sides of the last two sterilizing filters (1), and a heating filter is provided on the isolation tank; the three sterilizing filters (1) are all connected to the injection water pipeline, the pure steam pipeline, the nitrogen compressed air pipeline, the CIP cleaning supply pipeline, and the condensate discharge pipeline; a water receiving tray is provided below the three sterilizing filters (1), and the water receiving tray and the isolation tank are connected to the wastewater discharge pipeline; the three sterilizing filters (1) are provided with a pipeline test mirror, and the pipeline test mirror is connected to the condensate discharge pipeline; The sterilizing filter (1) in step 1 comprises a flow-dividing base (14), a filter housing (12) and a filter element (13); a sealing ring (17) is provided on the outer side of the upper end surface of the flow-dividing base (14); a sealing gasket (19), a screw-on groove and a plurality of screw-on protrusions (18) evenly distributed around the circumference are provided on the upper end surface of the flow-dividing base (14) and the lower end surface of the filter housing (12); a sealing groove is provided on the outer side of the lower end surface of the filter housing (12); when the flow-dividing base (14) and the filter housing (12) are screwed together, the sealing ring (17) is inserted into the sealing groove, the screw-on protrusions (18) are screwed into the corresponding screw-on grooves respectively, and the two sealing gaskets (19) are in contact with each other; an exhaust passage (15) and a filter element engaging hole (16) are provided on the upper end of the flow-dividing base (14); the filter element (13) is detachably screwed into the filter element engaging hole (16); and a pressure sensor and a temperature sensor are provided on the filter housing (12); The filter element replacement device in step eight comprises a hand-pushed mobile trolley (2), and the hand-pushed mobile trolley (2) is provided with a filter housing disassembly and assembly mechanism (3), a filter element switching mechanism (5) and a rotating placement mechanism (4) in sequence from left to right; The hand-pushed mobile trolley (2) comprises a vehicle body (6), a storage box (11) is fixed on the upper end of the vehicle body (6), a hand push rod (10) is fixed on the storage box (11), an electric lifting rod (7) is rotatably provided on the upper end of the vehicle body (6), a top plate (8) is fixed on the upper end of the electric lifting rod (7), and an avoidance notch (9) is opened on the top plate (8); The filter housing disassembly and assembly mechanism (3) comprises a transverse screw rod (20), the transverse screw rod (20) being fixed to the lower end of the top plate (8), and the transverse screw rod (20) being located on one side of the avoidance notch (9), a mounting frame plate (21) being provided on the transverse screw rod (20), a rotating motor (22) being fixed to the upper end of the mounting frame plate (21), an arc gear (23) being slidably provided on the lower end of the mounting frame plate (21), a driving gear being fixed to the output shaft of the rotating motor (22), the driving gear being meshed with the arc gear (23), a fixed base plate (26) being fixed to the lower end of the fixed base plate (26), a clamping cylinder (25) being fixed to the lower end of the fixed base plate (26), and two symmetrically arranged screwing jaws (24) being provided on the clamping cylinder (25); The filter element switching mechanism (5) comprises a fixing frame (27), the fixing frame (27) being fixed to the lower end of the top plate (8), and the fixing frame (27) being located on the other side of the avoidance gap (9), a lifting cylinder (28) being fixed to the fixing frame (27), a sliding base (29) being fixed to the telescopic end of the lifting cylinder (28), a rotating motor (30) being fixed to the sliding base (29), two sliding plates (31) being centrally symmetrically arranged being fixed to the output shaft of the rotating motor (30), and the sliding plates (31) being arranged so as to move in a direction opposite to the center of the sliding plate. An electric push plate (32) is fixed to each end, a rotation motor (36) is fixed to the upper end of the electric push plate (32), a rotation gear (35) is slidably provided at the lower end of the electric push plate (32), a rotating gear is fixed to the output shaft of the rotation motor (36), the rotating gear meshes with the rotation gear (35), a rotation base plate (34) is fixed to the lower end of the rotation base plate (34), a rotation cylinder (33) is fixed to the lower end of the rotation cylinder (33), and two symmetrically arranged rotation claws are provided on the rotation cylinder (33); The rotating placement mechanism (4) comprises an indexing motor (37), the indexing motor (37) being fixed to the lower end of the top plate (8), and the indexing motor (37) being located on the side of the fixed frame (27), a clamping base frame (38) being fixed to the output shaft of the indexing motor (37), a plurality of circumferentially evenly distributed engaging seats (39) being fixed to the clamping base frame (38), two symmetrically arranged clamping claws (40) being rotatably provided on the engaging seat (39), and a tension spring being provided between the ends of the clamping claws (40) and the engaging seat (39).

2. The online integrity detection process for a parallel two-stage sterilizing filter element according to claim 1 is characterized in that: The injection water pipeline, pure steam pipeline, nitrogen compressed air pipeline, CIP cleaning supply pipeline, condensate discharge pipeline, CIP cleaning discharge pipeline, wastewater discharge pipeline, material conveying pipeline, and material circulation pipeline are all inclined pipelines with the feed end higher than the discharge end.

Images