Sterile filter integrity test device

Abstract

The application discloses a kind of sterilizing filter integrity test device, the sterilizing filter integrity test device includes: integrity tester, the integrity tester, the integrity tester is used to communicate compressed air;First filter, the first filter is communicated with the integrity tester by pipeline, and the first filter is used to filter gas;Second filter, the second filter is communicated with the first filter by pipeline, and the second filter is used to filter liquid;Buffer tank, the inlet of buffer tank is communicated with the second filter by pipeline, and the outlet of buffer tank is communicated with drain line by pipeline, and the pipeline of two components communicated is equipped with the valve door.The sterilizing filter integrity test device of the present application can avoid the risk of secondary pollution in offline testing and the risk of filter damage during work station transfer, and can improve the detection efficiency and the reliability of experimental results.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of aseptic preparation liquid preparation system, in particular to a sterilization filter integrity testing device. BACKGROUND

[0002] With the development of pharmaceutical production technology, an aseptic preparation liquid preparation system appears. In the aseptic preparation liquid preparation system, a sterilization filter is usually the last guarantee for whether a drug sterile index meets a standard, and whether a terminal sterilization filter cartridge is intact is also an important reference for measuring whether the batch of drugs is qualified. Therefore, how to detect the integrity of the sterilization filter cartridge is an extremely important step of detection process. The current Good Manufacturing Practice (GMP) requires that the sterilization filter needs to be tested for integrity after use.

[0003] In the traditional technology, the current integrity detection method in the industry is divided into offline integrity detection (removing the sterilization filter to a designated position for integrity detection) and in-situ detection of the sterilization filter (the sterilization filter does not need to be transferred to the position, and the integrity detection is performed at the filtering position). However, the current offline integrity detection has defects such as inconvenient filter cartridge wetting, risk of secondary pollution after detection, and the like. The in-situ detection also has imperfect process flow during wetting and detection, and not strict risk control during the detection process. SUMMARY

[0004] Therefore, it is necessary to provide a sterilization filter integrity testing device which can effectively improve the integrity detection efficiency of the sterilization filter and avoid secondary pollution.

[0005] The technical scheme is as follows: a sterilization filter integrity testing device, the sterilization filter integrity testing device comprises: an integrity tester, the integrity tester is used for communicating compressed air; a first filter, the first filter is communicated with the integrity tester through a pipeline, and the first filter is used for filtering gas; a second filter, the second filter is communicated with the first filter through a pipeline, and the second filter is used for filtering liquid; a buffer tank, an inlet of the buffer tank is communicated with the second filter through a pipeline, and an outlet of the buffer tank is communicated with a blowdown pipeline through a pipeline; and a valve, a plurality of valves are arranged on the pipelines of two connected components.

[0006] The integrity test device of the sterilization filter has the advantages that when the integrity test of the aseptic preparation solution preparation system is needed, the integrity tester is connected to the system, the related valves are opened, the compressed air for test is introduced, the compressed air flows through the integrity tester and then flows through the first filter to filter the test gas, which is beneficial to guarantee that the filtered gas is hygienic compressed air and to prevent secondary pollution of the system. Then, the filtered gas enters the second filter to test the integrity of the second filter, the test data is monitored and determined by the integrity tester, part of the test gas enters the buffer tank, the liquid in the buffer tank is discharged to guarantee the stability of the pressure and to guarantee that the liquid always exists in the buffer tank to prevent the reverse pollution of the medium in the discharge pipeline to the system and to play a blocking role. The integrity test device of the sterilization filter is beneficial to avoid the risk of secondary pollution in offline test and the risk of damage of the filter element in the process of station transfer, and is beneficial to improve the detection efficiency and the reliability of the experimental results.

[0007] In one of the embodiments, the buffer tank is provided with a first sensor and a second sensor, the first sensor and the second sensor are arranged at intervals along the height direction of the buffer tank, and the first sensor and the second sensor are both used for detecting the liquid level height in the buffer tank.

[0008] In one of the embodiments, the integrity test device of the sterilization filter further comprises a third filter, the third filter is communicated with the inlet of the buffer tank through a pipeline, and the third filter is used for filtering and discharging the gas.

[0009] In one of the embodiments, the buffer tank is provided with a spray ball, and the spray ball is communicated with the inlet of the buffer tank.

[0010] In one of the embodiments, the integrity test device of the sterilization filter further comprises a heat exchanger, the inlet of the heat exchanger is used for communicating with the water for injection, the outlet of the heat exchanger is communicated with the second filter through a pipeline, and the port, through which the second filter is communicated with the first filter, is further used for communicating with the blowdown pipeline through a pipeline.

[0011] In one of the embodiments, the integrity test device of the sterilization filter further comprises a first pressure sensor and a second pressure sensor, the first pressure sensor is communicated on the pipeline between the heat exchanger and the second filter, and the second pressure sensor is communicated on the pipeline between the second filter and the buffer tank.

[0012] In one of the embodiments, the inlet of the heat exchanger is further used for communicating with a compressed air device through a pipeline.

[0013] In one of the embodiments, the heat exchanger is provided with a chilled water inlet for the incoming chilled water and a chilled water outlet for the outgoing chilled water, a first proportional regulating angular valve is arranged on the pipeline of the chilled water outlet, and a first temperature sensor is arranged on the pipeline between the heat exchanger and the second filter, and the first temperature sensor is electrically connected with the first proportional regulating angular valve.

[0014] In one of the embodiments, the heat exchanger is further provided with a Y-type filter, which is arranged on the pipeline of the chilled water inlet and used for filtering the liquid.

[0015] In one of the embodiments, the first filter is provided with a first port, a second port and a third port, the first port is communicated with the second filter, the second port and the third port are communicated with the pure steam condensate discharge pipeline through the pipeline, a second temperature sensor is arranged between the second port and the pure steam condensate discharge pipeline, the third filter is provided with a fourth port, a fifth port and a sixth port, the fourth port is communicated with the inlet of the buffer tank, the fifth port and the sixth port are communicated with the pure steam condensate discharge pipeline through the pipeline, a third temperature sensor is arranged between the fourth port and the pure steam condensate discharge pipeline, the outlet of the buffer tank is further communicated with the pure steam condensate discharge pipeline, and a fourth temperature sensor is arranged between the outlet of the buffer tank and the pure steam condensate discharge pipeline. BRIEF DESCRIPTION OF DRAWINGS

[0016] The accompanying drawings, which form a part of the present application, are intended to provide further understanding of the present application, and are used to interpret the specific embodiments of the present application and their descriptions, and do not constitute improper limitations to the present application.

[0017] In order to more clearly illustrate the technical solutions in the embodiments of the present application, the accompanying drawings needed to be used in the embodiment description will be briefly introduced. Obviously, the accompanying drawings in the following description only constitute some embodiments of the present application, and other accompanying drawings can be obtained by those skilled in the art without any creative effort on the basis of these accompanying drawings.

[0018] Figure 1 A working principle diagram of the sterilization filter integrity test device in one of the embodiments;

[0019] Figure 2 A CIP online cleaning process schematic diagram in one of the embodiments;

[0020] Figure 3 A SIP pure steam sterilization process schematic diagram in one of the embodiments;

[0021] Figure 4A schematic diagram of the pre-test wetting process described in one embodiment;

[0022] Figure 5 A schematic diagram of the integrity test process described in one embodiment;

[0023] Figure 6 A schematic diagram of the post-test purge evacuation process described in one embodiment.

[0024] BRIEF DESCRIPTION OF DRAWINGS

[0025] 100, sterilizing filter integrity test device; 110, integrity tester; 120, first filter; 130, second filter; 131, first pressure sensor; 132, second pressure sensor; 140, buffer tank; 141, first sensor; 142, second sensor; 143, third filter; 144, spray ball; 150, heat exchanger; 151, first temperature sensor; 152, first proportional control angle valve; 153, Y-type filter; 154, second temperature sensor; 155, third temperature sensor; 156, fourth temperature sensor; 11, circulating injection water inlet; 12, circulating injection water outlet; 21, pure steam inlet; 31, clean compressed air; 41, circulating chilled water return; 42, circulating chilled water inlet; 51, test compressed air inlet; 61, material inlet / CIP outlet; 62, material outlet / CIP outlet; 71, pure steam condensate discharge; 81, blowdown line. DETAILED DESCRIPTION

[0026] In order to make the above objectives, features and advantages of the present application more apparent, specific embodiments of the present application will be described in detail below with reference to the accompanying drawings. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present application. It will be apparent, however, to one skilled in the art that the present application can be practiced without using some or all of these specific details. In other instances, well-known process steps have not been described in detail in order to avoid obscuring the present application. Accordingly, the specific embodiments disclosed below do not define or constrain the scope of the application.

[0027] In the description of the present application, it should be understood that the terms "center", "longitudinal", "transverse", "length", "width", "thickness", "upper", "lower", "front", "back", "left", "right", "vertical", "horizontal", "top", "bottom", "inner", "outer", "clockwise", "counterclockwise", "axial", "radial", "circumferential" and the like indicate the orientation or positional relationship based on the orientation or positional relationship shown in the drawings, and are only for the convenience of describing the present application and simplifying the description, and therefore cannot be understood as indicating or implying that the device or element referred to must have a particular orientation, be constructed and operated in a particular orientation, and therefore cannot be understood as limiting the present application.

[0028] In addition, the terms "first", "second", etc. are used herein only to describe different instances, and are not used to denote or imply relative importance or a number of indicated technical features. Thus, features defined with "first", "second", etc. can explicitly or implicitly include at least one of the features. In the description of the present application, the meaning of "a plurality of" is at least two, such as two, three, etc., unless otherwise explicitly specified and limited.

[0029] In the present application, unless otherwise explicitly specified and limited, the terms "mounting", "connecting", "connecting", "fixing" and the like should be understood broadly, for example, it can be fixedly connected, or it can be detachably connected, or it can be integrated; it can be mechanically connected, or it can be electrically connected; it can be directly connected, or it can be indirectly connected through an intermediate medium; it can be the internal communication of two elements or the interaction relationship between two elements, unless otherwise explicitly limited. For those skilled in the art, the specific meaning of the above terms in the present application can be understood according to the specific circumstances.

[0030] In the present application, unless otherwise explicitly specified and limited, the first feature is "on" or "under" the second feature, which can be direct contact between the first and second features, or indirect contact between the first and second features through an intermediate medium. Moreover, the first feature "above", "over" and "on" the second feature can be directly above or obliquely above the first feature, or only indicate that the horizontal height of the first feature is higher than that of the second feature. The first feature "below", "under" and "under" the second feature can be directly below or obliquely below the first feature, or only indicate that the horizontal height of the first feature is less than that of the second feature.

[0031] It should be noted that when an element is referred to as "fixed to" or "disposed on" another element, it can be directly on the other element or there can be a middle element. When an element is referred to as "connected to" another element, it can be directly connected to the other element or there can be a middle element. The terms "vertical", "horizontal", "up", "down", "left", "right" and similar expressions used herein are for illustrative purposes only and are not the only embodiment.

[0032] Please refer to Figure 1 With Figure 5 , Figure 1 The working principle diagram of the sterilization filter integrity test device 100 in an embodiment of the present application is shown; Figure 5The integrity test flowchart in the embodiment of the present application is shown, and the integrity test device 100 for the sterilizing filter provided by the embodiment of the present application comprises: an integrity tester 110, a first filter 120, a second filter 130, a buffer tank 140 and valves. The integrity tester 110 is used for communicating compressed air. The integrity tester 110 is used for performing integrity test on the first filter 120. The first filter 120 is communicated with the integrity tester 110 through a pipeline, and the first filter 120 is used for filtering gas. For example, the first filter 120 is a gas filter. The second filter 130 is communicated with the first filter 120 through a pipeline, and the second filter 130 is used for filtering liquid. The second filter 130 is a liquid filter. The inlet of the buffer tank 140 is communicated with the second filter 130 through a pipeline, and the outlet of the buffer tank 140 is communicated with a blowdown pipeline 81. The valves are multiple, and each pipeline of two connected components is provided with a valve.

[0033] During the working process of the above-mentioned integrity test device 100 for the sterilizing filter, when the integrity test on the aseptic preparation liquid preparation system is needed, the integrity tester 110 is connected to the system, the related valves are opened, the test compressed air is introduced, the compressed air flows through the integrity tester 110, and then flows through the first filter 120 to perform sterilizing filtration on the test gas, which is beneficial to guarantee that the filtered gas is sanitary grade compressed air and to prevent secondary pollution of the system. Then, the filtered gas enters the second filter 130 to perform integrity test on the second filter 130, the test data is monitored and determined whether it is qualified by the integrity tester 110, part of the test gas enters the buffer tank 140, the liquid in the buffer tank 140 is discharged, so as to guarantee the stability of the pressure and to guarantee that there is always liquid in the buffer tank 140, thereby avoiding the reverse pollution of the medium in the blowdown pipeline to the system and playing a blocking role. The integrity test device 100 for the sterilizing filter is beneficial to avoid the secondary pollution risk of offline test and the risk of damage of the filter element in the process of station transfer, and is beneficial to improve the detection efficiency and the reliability of the experimental results.

[0034] Since the specific structure and working mode of the integrity tester 110 are not the improvement points of the present application, the present application does not specifically limit the structure and working principle of the integrity tester, as long as the integrity test on the filter is met, and the specific structure and working principle of the integrity tester can be referred to the existing integrity tester 110 equipment.

[0035] Specifically, when the integrity test device 100 for the sterilizing filter performs integrity test on the filter, the complete process flow can be in sequence: CIP online cleaning process, SIP pure steam sterilization process, pre-test wetting process, integrity test process and post-test purging and emptying process.

[0036] In one embodiment, referring to Figure 1 The buffer tank 140 is provided with a first sensor 141 and a second sensor 142. The first sensor 141 and the second sensor 142 are arranged in a height direction of the buffer tank 140, and both are used to detect the liquid level in the buffer tank 140. For example, both the first sensor 141 and the second sensor 142 are liquid level sensors. Through the first sensor 141 and the second sensor 142, the liquid level in the buffer tank 140 can be detected during the integrity test process. If the liquid level in the buffer tank 140 rises to the monitoring position of the first sensor 141 during the test process, the corresponding valve at the outlet of the buffer tank 140 is opened in sequence to discharge the liquid in the tank at a high liquid level. When the liquid level is discharged to the monitoring position of the second sensor 142, the corresponding discharge valve of the buffer tank 140 is closed, and the liquid level discharge process in the buffer tank 140 is repeated in sequence according to the liquid level in the tank. In this way, it is beneficial to automatically discharge the liquid and ensure the buffering effect of the buffer tank 140, thereby avoiding the backflow of the medium in the lower discharge pipeline.

[0037] In one embodiment, referring to Figure 1 The sterilizing filter integrity test device 100 further comprises a third filter 143, which is communicated with the inlet of the buffer tank 140 through a pipeline, and is used to filter and discharge gas. For example, the third filter 143 is a gas filter. In this way, during the integrity test, the test gas can be filtered through the third filter 143 before being discharged, which is beneficial to meet the requirements of gas discharge.

[0038] In one embodiment, referring to Figure 1 The buffer tank 140 is provided with a spray ball 144, which is communicated with the inlet of the buffer tank 140. In this way, during the CIP online cleaning, after the water for injection enters the buffer tank 140, the spray ball 144 can be used to clean the buffer tank 140 through the spray effect. During the low-temperature wetting process of the test chamber, the low-temperature water for injection can be used to wet the buffer tank 140 through the spray ball 144, which is beneficial to improve the work efficiency.

[0039] In one embodiment, referring to Figure 1 The sterilizing filter integrity test device 100 further comprises a heat exchanger 150, the inlet of which is used to communicate with the water for injection, and the outlet of which is communicated with the second filter 130 through a pipeline. Moreover, the port of the second filter 130 communicated with the first filter 120 is also used to communicate with the blowdown pipeline 81 through a pipeline. In this way, the heat exchanger 150 can change the temperature of the water for injection, so as to meet the temperature requirements of the CIP online cleaning and the SIP pure steam sterilization. Moreover, during the pre-test wetting process, the heat exchanger 150 can reduce the outlet water temperature, so as to meet different wetting requirements.

[0040] In one embodiment, referring to Figure 1 , the sterilizing filter integrity test device 100 further comprises a first pressure sensor 131 and a second pressure sensor 132. The first pressure sensor 131 is connected to the pipeline between the heat exchanger 150 and the second filter 130, and the second pressure sensor 132 is connected to the pipeline between the second filter 130 and the buffer tank 140. In this way, in the SIP pure steam sterilization process, when a proportional regulating angle valve is provided between the heat exchanger 150 and the second filter 130, the proportional regulating angle valve can adjust the opening proportion of the valve online according to the pressure difference between the first pressure sensor 131 and the second pressure sensor 132, so that the difference between the first pressure sensor 131 and the second pressure sensor 132 is within a predetermined range, avoiding damage to the filter element of the second filter 130 caused by high temperature and high pressure, and ensuring the working reliability of the sterilizing filter integrity test device 100.

[0041] In one embodiment, the inlet of the heat exchanger 150 is also used to connect the compressed air equipment through the pipeline. In this way, after the integrity test process, the compressed air equipment can be connected to perform a test and purge emptying process on all components in the system, ensuring that the system is in a dry state and avoiding the risk of microbial growth caused by residual water.

[0042] In one embodiment, the heat exchanger 150 is provided with a chilled water inlet and a chilled water outlet. The chilled water inlet is used to introduce chilled water, and the chilled water outlet is used to return the chilled water. A first proportional regulating angle valve 152 is provided on the pipeline of the chilled water outlet, and a first temperature sensor 151 is further provided on the pipeline between the heat exchanger 150 and the second filter 130. The first temperature sensor 151 is electrically connected to the first proportional regulating angle valve 152. In this way, when the heat exchanger 150 is used to humidify the high-temperature test before the process, the first temperature sensor 151 can inject water for heat exchange and cooling. During the cooling process, the first proportional regulating angle valve 152 is linked to the first temperature sensor 151 for linkage control, so as to accurately control the water temperature of the heat exchanger 150 to be less than a predetermined temperature. During the initial stage of heat exchange, when the temperature value is greater than the predetermined temperature, the relevant valve is opened for high-temperature water discharge. When the temperature value of the first temperature sensor 151 is less than or equal to the predetermined temperature, the relevant valve is closed to humidify the filter element in the second filter 130 at a low temperature.

[0043] In one embodiment, referring to Figure 1 , the heat exchanger 150 is further provided with a Y-type filter 153. The Y-type filter 153 is connected to the pipeline of the chilled water inlet, and is used to filter the liquid. In this way, during the humidification process before the test, the Y-type filter 153 can filter the chilled water to ensure the chilling effect of the chilled water and the service life of the heat exchanger 150.

[0044] In one embodiment, referring to Figure 1 , referring to Figure 2 , the first filter 120 is provided with a first port, a second port and a third port, the first port is communicated with the second filter 130. The second port and the third port are communicated with the pure steam condensate discharge 71 pipeline through a pipeline, and a second temperature sensor 154 is arranged between the second port and the pure steam condensate discharge 71 pipeline. The third filter 143 is provided with a fourth port, a fifth port and a sixth port, the fourth port is communicated with the inlet of the buffer tank 140. The fifth port and the sixth port are communicated with the pure steam condensate discharge 71 pipeline through a pipeline, and a third temperature sensor 155 is arranged between the fourth port and the pure steam condensate discharge 71 pipeline. The outlet of the buffer tank 140 is also communicated with the pure steam condensate discharge 71 pipeline, and a fourth temperature sensor 156 is arranged between the outlet of the buffer tank 140 and the pure steam condensate discharge 71 pipeline. In this way, in the SIP steam sterilization process, the temperatures in the system can be detected by the second temperature sensor 154, the third temperature sensor 155 and the fourth temperature sensor 156 at the same time, when the temperatures of the three groups of temperature sensors all exceed the preset temperature, the SIP pure steam sterilization starts in time and lasts for a period of time, then it is determined that the sterilization is qualified, and the sterilization process is ended. If the temperature value of any one of the three groups of temperature sensors is less than the preset temperature during the sterilization process, the entire sterilization process starts again until the sterilization is qualified. In this way, it is beneficial to automatically monitor the sterilization effect and improve the sterilization efficiency.

[0045] In one embodiment, the specific working process of the sterilization filter integrity test device 100 is as follows:

[0046] Firstly, the CIP (clean in place) online cleaning process is started, referring to Figure 2 , Figure 2 The CIP online cleaning process is shown in the embodiment of the application; wherein the CIP online cleaning process includes tangential flow cleaning and vertical flow cleaning. In the tangential flow cleaning, the water for injection comes from the water for injection circulating pipeline, the relevant valves are opened, the water for injection passes through the double-tube plate heat exchanger 150 to perform tangential flow cleaning on the second filter 130 and the pipeline valve along the way, to clean the impurities attached to the surface of the filter element, and the cleaning is finally judged according to whether the conductivity detection index of the liquid preparation system terminal meets the conductivity index of the water for injection (≤2.5 us / cm@70℃), if qualified, the vertical flow cleaning program is entered.

[0047] Referring to Figure 4, in the vertical flow cleaning, the water for injection is from the water for injection circulating pipeline, the valve in the pipeline is opened, the double tube plate heat exchanger 150 is passed through, the diaphragm valve is opened, the proportional adjusting diaphragm valve is opened, the second filter 130 is passed through, the diaphragm valve is opened, the spray ball 144 is passed through, the buffer tank 140 is passed through, the diaphragm valve is opened, the ball valve is opened, and the second filter 130, the buffer tank 140 and the pipeline valve along the way are vertically cleaned through the related pipeline, and the final judgment basis is that the terminal conductivity detection index of the preparation system meets the conductivity index of the water for injection (≤2.5 us / cm @ 70 DEG C). If it is qualified, it enters the SIP pure steam sterilization process.

[0048] The SIP pure steam sterilization process: the pure steam comes from the pure steam distribution system pipeline network, the ball valve is opened, the diaphragm valve is opened, the double tube plate heat exchanger 150 is passed through, the diaphragm valve is opened, the proportional adjusting diaphragm valve is opened, wherein the proportional adjusting diaphragm valve adjusts the valve opening proportion on line according to the difference between the first pressure sensor 131 and the second pressure sensor 132, guarantees that the difference between the two pressure sensors is ≤0.3 bar, and avoids filter core damage caused by high temperature and high pressure. The branch diaphragm valve is opened synchronously, the non-condensable gas & condensate water discharge before the sterilization filter is discharged through the drain valve. Then the pure steam synchronously flows through the second filter 130, the two diaphragm valves on the route are opened synchronously, the ball valve is opened, and the non-condensable gas & condensate water discharge in the cavity of the first filter 120 is discharged through the drain valve. Then the pure steam synchronously flows through the opened diaphragm valve, passes through the gas sterilization filter, opens the ball valve, and discharges the non-condensable gas & condensate water in the cavity of the first filter 120 through the drain valve. Then the pure steam synchronously flows through the opened diaphragm valve, passes through the spray ball 144, passes through the buffer tank 140, opens the diaphragm valve, opens the ball valve, and discharges the non-condensable gas & condensate water in the buffer tank 140 through the drain valve. Then, the pure steam synchronously flows through the opened diaphragm valve, passes through the third filter 143, opens the ball valve, and discharges the non-condensable gas & condensate water in the cavity of the third filter 143 through the drain valve.

[0049] All the fittings in the whole device are sterilized by pure steam, and the temperature in the system is monitored by the first temperature sensor 151, the second temperature sensor 154 and the third temperature sensor 155 during the sterilization process. When the temperature values of the three groups of temperature sensors are all ≥121 DEG C, the sterilization timing starts, and the sterilization process is ended when the temperature value is continuously maintained above 121 DEG C for more than 20 min. If the temperature value of any one of the three groups of temperature sensors is <121 DEG C during the sterilization process, the whole sterilization process starts again until the sterilization is qualified. After the sterilization process is ended, the next pre-wetting process is entered.

[0050] Please refer to Figure 4 , Figure 4For the pre-test wetting process described in an embodiment, the pre-test wetting process, the water for injection is derived from the water for injection network, for example, the water for injection is about 80℃, in use, according to Figure 5 The arrow on the pipe is opened in the direction, the diaphragm valve is opened, the water for injection flows through the heat exchanger 150. At the same time, the ball valve is opened, passes through the Y type filter 153, the ball valve is opened, the proportional regulating angle valve is opened, the ball valve is opened, the above-mentioned valve is opened to the shell side of the heat exchanger 150, and the 7℃ refrigerated water is introduced to cool the high temperature water for injection. The proportional regulating angle valve and the first temperature sensor 151 are linked to control the water temperature of the heat exchanger 150 ≤40℃ during the cooling process. At the initial stage of heat exchange, when the temperature value of the first temperature sensor 151 is >40℃, the valve is opened to discharge the high temperature water, so as to avoid the high temperature water entering the second filter 130. When the temperature value of the first temperature sensor 151 is ≤40℃, the diaphragm valve is closed, and the diaphragm valve is opened in turn, the proportional regulating diaphragm valve is opened, flows through the second filter 130, the diaphragm valve is opened, and flows through the spray ball 144. The above process can wet the filter element in the second filter 130 at low temperature, and the wetting time can be set in the program. In this way, filter elements of different sizes can be wetted, and the wetted water for injection is discharged into the buffer tank 140 through the first sensor 141 and then the second sensor 142 to monitor the high and low liquid level in the tank. When the liquid level reaches the position of the first sensor 141, the diaphragm valve and the ball valve below the tank are opened in turn to discharge the high liquid level. When the liquid level reaches the position of the second sensor 142, the tank valve is closed, and the discharge is completed. The liquid level discharge process is repeated according to the liquid level in the tank. The purpose is to keep the "water seal" in the buffer tank 140 during the integrity test, which can avoid the reverse pollution of the medium in the lower discharge pipeline to the system, and plays a blocking role. After the pre-test wetting process is completed, the next step integrity test process is entered.

[0051] Please refer to Figure 5 , Figure 5 The integrity test process described in an embodiment of the application is shown in the schematic diagram; in the integrity test process, the integrity tester 110 is connected to the system, according to Figure 6Following the arrow direction in the central pipeline, the ball valve is opened sequentially to introduce test compressed air. The compressed air flows through the integrity tester 110, then the ball valve is opened again, and the air flows through the third filter 143. The function of the third filter 143 is to perform terminal sterilization filtration on the test compressed air, ensuring that all compressed air entering the module is sanitary compressed air, preventing secondary contamination of the system. Then, the diaphragm valve is opened, and the test gas enters the second filter 130 to perform an integrity test on the second filter 130. The test data is monitored and judged by the integrity tester 110 to determine whether it is qualified. Simultaneously, the diaphragm valve, the ball valve, and the diaphragm valve are opened. During the test, exhaust is performed through the third filter 143. If the liquid level in the integrity test buffer tank 140 rises to the position of the first sensor 141 during the test, the diaphragm valve and the ball valve at the bottom of the tank are opened sequentially to discharge the high liquid level. When the liquid level reaches the position of the second sensor 142, the valve at the bottom of the tank is closed, and the discharge ends. The liquid level discharge process in the tank is repeated sequentially according to the liquid level in the tank. The integrity test buffer tank 140 always maintains a "water seal" to prevent the medium in the downstream pipeline from back-contaminating the system, thus playing a barrier role; after the integrity test process is completed, the next test purging and emptying process begins.

[0052] Please see Figure 6 , Figure 6 This diagram illustrates a post-test purging and venting process according to an embodiment of the present invention. After integrity testing, residual water for injection is inevitable in the system. To prevent microbial growth in the residual water and its impact on the effective component content of the initial drug solution, this post-test purging and venting process is designed to address this issue. Specifically, the purging process involves 3 bar clean compressed air 31 sourced from the clean compressed air 31 distribution system pipeline, according to... ​ The central pipeline opens the ball valve, diaphragm valve, heat exchanger 150, diaphragm valve, proportional regulating diaphragm valve, second filter 130, diaphragm valve, spray ball 144, buffer tank 140, and ball valve in sequence. By opening the above valves, a positive pressure purging and venting process for clean compressed air is achieved. After purging, the system is kept dry to avoid risks such as residual water and microbial growth.

[0053] The sterilizing filter integrity test device 100 is advantageous to solve the secondary pollution risk of the filter in the operation process of the low-temperature water for injection wetting (≤40℃), the connection of the compressed air pipeline above 6bar, the secondary connection of the filter station after the test is completed, and the mis-detection risk caused by the accidental damage of the filter core in the station transfer process. Moreover, it is advantageous to solve the secondary risk of the wetting water residue in the wetting process of the filter core in the previous in-situ integrity test, the reverse secondary pollution risk in the test process, and the secondary pollution risk caused by the hygiene quality problem of the high-pressure compressed air for test. In addition, the design of the sterilizing filter integrity test device 100 is modular and flexible, and the sterilizing filter therein can be selected according to the liquid filling flow requirement. The buffer tank 140 volume can also be selected according to the filter core wetting water requirement to provide different volumes. The module can be applied to the filling and filtering and integrity test of any sterile preparation liquid preparation system, and the modular design structure is compact and occupies small space, which can reduce the air conditioning energy consumption of the pharmaceutical purification area, and is convenient for transportation, installation and operation and maintenance.

[0054] The technical features of the above-described embodiments can be combined in any manner. To make the description concise, all possible combinations of the technical features in the above-described embodiments are not described, but as long as the combinations of the technical features do not exist, they should be considered as the scope of the present disclosure.

[0055] The above-described embodiments only express several embodiments of the present application, and the description is more specific and detailed, but it should not be understood as a limitation on the scope of the patent. It should be pointed out that for ordinary skilled in the art, without departing from the concept of the present application, a number of variations and improvements can be made, which are within the scope of the present application. Therefore, the scope of protection of the present application should be subject to the appended claims.

Claims

1. A bacteriological filter integrity testing device characterized by, The bacteria-removing filter integrity test device comprises: an integrity tester, which is used to communicate with compressed air; a first filter, which is used to filter gas and is communicated with the integrity tester through a pipeline; a second filter, which is used to filter liquid and is communicated with the first filter through a pipeline; a buffer tank, an inlet of which is communicated with the second filter through a pipeline, and an outlet of which is communicated with a blowdown pipeline through a pipeline; valves, which are provided on the pipelines of two communicating components; the buffer tank is provided with a first sensor and a second sensor, which are arranged at intervals along the height direction of the buffer tank, and are used to detect the liquid level height in the buffer tank; the bacteria-removing filter integrity test device further comprises a third filter, which is used to filter and discharge gas and is communicated with the inlet of the buffer tank through a pipeline; the buffer tank is provided with a spray ball, which is communicated with the inlet of the buffer tank; the bacteria-removing filter integrity test device further comprises a heat exchanger, an inlet of which is used to communicate with water for injection, an outlet of which is communicated with the second filter through a pipeline, and the port of the second filter communicated with the first filter is further used to communicate with the blowdown pipeline through a pipeline; the bacteria-removing filter integrity test device further comprises a first pressure sensor and a second pressure sensor, the first pressure sensor is communicated on the pipeline between the heat exchanger and the second filter, and the second pressure sensor is communicated on the pipeline between the second filter and the buffer tank.

2. The integrity test device for a bacteria removing filter according to claim 1, characterized in that, the inlet of the heat exchanger is further used to communicate with a compressed air device through a pipeline.

3. The integrity test device for a bacteria removing filter according to claim 1, characterized in that, the heat exchanger is provided with a chilled water inlet and a chilled water outlet, the chilled water inlet is used to introduce chilled water, the chilled water outlet is used to return water, a first proportional regulating angle valve is provided on the pipeline of the chilled water outlet, a first temperature sensor is further provided on the pipeline between the heat exchanger and the second filter, and the first temperature sensor is electrically connected with the first proportional regulating angle valve.

4. The integrity test device for a bacteria removing filter according to claim 3, characterized in that, the heat exchanger is further provided with a Y-type filter, which is communicated on the pipeline of the chilled water inlet and is used to filter liquid.

5. The integrity test device for a bacteria removing filter according to claim 3, characterized in that, The first filter is provided with a first port, a second port and a third port, the first port is communicated with the second filter, the second port and the third port are communicated with the pure steam condensate water discharge pipeline through a pipeline, a second temperature sensor is arranged between the second port and the pure steam condensate water discharge pipeline, the third filter is provided with a fourth port, a fifth port and a sixth port, the fourth port is communicated with the inlet of the buffer tank, the fifth port and the sixth port are communicated with the pure steam condensate water discharge pipeline through a pipeline, a third temperature sensor is arranged between the fourth port and the pure steam condensate water discharge pipeline, the outlet of the buffer tank is also communicated with the pure steam condensate water discharge pipeline, and a fourth temperature sensor is arranged between the outlet of the buffer tank and the pure steam condensate water discharge pipeline.

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