Influenza vaccine semi-finished product degerming system and influenza vaccine semi-finished product degerming process
Patent Information
- Application Number
- CN202511038777.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-07-28
- Publication Date
- 2025-09-23
Smart Images
Figure CN120679228A_ABST
Abstract
Description
Technical Field
[0001] The present application belongs to the field of vaccine production technology, and specifically relates to a semi-finished influenza vaccine sterilization system and a semi-finished influenza vaccine sterilization process. Background Art
[0002] The flu vaccine is used to prevent influenza (also known as the flu), which is caused by influenza viruses. It is an inactivated influenza vaccine composed of three different viruses. The flu vaccine is one of the main measures for preventing and controlling influenza, reducing the chance of contracting the flu or alleviating flu symptoms.
[0003] After the virus is inactivated, lysed and purified, human serum albumin is added to form a stock solution. The stock solution becomes a semi-finished product after preparation. The semi-finished product contains impurities or microorganisms and needs to be filtered. The existing filtration is through a bag filter, which allows the drug solution to pass through the filter membrane of the bag filter. During filtration, the filter element needs to be replaced regularly to ensure that the impurities in the vaccine are filtered out. However, the integrity of the filter element cannot be confirmed in time, which may easily cause impurities in the filtered raw materials, poor filtration effect, impurities will contaminate the raw materials, and affect the quality of the vaccine; bag filters are generally used for repeated filtration, and the size of the impurities screened is limited to a certain range. If the filtered raw materials contain impurities, the raw material particles will be of different sizes, which may easily cause poor vaccine stability and stratification. Large particles will cause the vaccine to have high viscosity, which is not conducive to injection. Summary of the Invention
[0004] The embodiments of the present application provide a system and process for sterilizing influenza vaccine semi-finished products, aiming to solve the technical problems of the prior art vaccine semi-finished products, such as poor filtration effect, limitations, inability to replace the filter element in time, contamination of the semi-finished product, affecting the quality of the vaccine, and difficulty in injection.
[0005] To achieve the above objectives, the technical solution adopted in this application is: In a first aspect, a system for sterilizing semi-finished influenza vaccines is provided, comprising: A sterile box having a liquid inlet pipe on one side and a liquid outlet pipe on the other side; A first filter assembly is disposed in the sterile box, wherein the liquid inlet of the first filter assembly is connected to the outlet of the liquid inlet pipe, and the first filter assembly has a first filter element; a second filter assembly disposed in the sterile box, wherein the liquid inlet of the second filter assembly is connected to the liquid outlet of the first filter assembly, and the liquid outlet of the second filter assembly is connected to the inlet of the liquid outlet pipe, the second filter assembly comprises a second filter element, and the filtration accuracy of the first filter element is lower than that of the second filter element; and A monitoring system is provided in the sterile box, and the monitoring system is used to monitor the integrity of the first filter element and the second filter element.
[0006] In conjunction with the first aspect, in one possible implementation, the inlet of the liquid inlet pipe is connected to a medicine pipe, and semi-finished liquid medicine flows in the medicine pipe; the liquid inlet pipe is also connected to a steam pipe and a first medium pipe respectively, and the first medium pipe is used to pass a cleaning agent or a disinfectant; The outlet of the liquid outlet pipe is also connected to a second medium pipe, and the second medium pipe is used to discharge cleaning agent or disinfectant.
[0007] In conjunction with the first aspect, in a possible implementation, the first filtering system further includes: a first filter installed in the sterile box, wherein the bottom inlet of the first filter is connected to the liquid inlet pipe, the first filter element is installed in the first filter, and the top of the first filter is provided with a first exhaust port; A first buffer is installed in the sterile box, and a bottom outlet of the first buffer is connected to the second filtering system; and The first communicating pipe has two ends respectively connected to the bottom inlet of the first buffer and the bottom outlet of the first filter. One end of the first communicating pipe close to the first filter is connected to the first discharge port.
[0008] In combination with the first aspect, in a possible implementation, a first tube is provided at the top of the first buffer, the first tube extends downward into the first buffer, and a first spray ball is provided at the bottom, the first tube is used to introduce a cleaning agent or disinfectant into the first buffer; a second discharge port is opened at the bottom of the first buffer.
[0009] With reference to the first aspect, in a possible implementation, the first filter includes: a shell, installed in the sterile box, the top of the shell being provided with the first exhaust port; and A fixing frame is arranged inside the shell, and a vertically extending filter channel is formed inside the fixing frame. The central axis of the filter channel overlaps with the central axis of the shell. The first filter element is installed in the filter channel. The bottom end of the filter channel is connected to the first connecting pipe, and the outlet of the liquid inlet pipe is connected to the bottom of the shell.
[0010] In conjunction with the first aspect, in a possible implementation, the second filtering system further includes: a second filter installed in the sterile box, wherein the bottom inlet of the second filter is connected to the outlet of the first filter assembly, the second filter element is installed in the second filter, and the top of the second filter is provided with a second exhaust port; A second buffer is installed in the sterile box, and a bottom outlet of the second buffer is connected to the inlet of the liquid outlet pipe; and The second communicating pipe has two ends respectively connected to the bottom inlet of the second buffer and the bottom outlet of the second filter. The two ends of the second communicating pipe close to the second filter are connected to the third outlet.
[0011] In conjunction with the first aspect, in one possible implementation, a second tube is provided at the top of the second buffer, the bottom of the second tube extends into the second buffer, and a second spray ball is provided at the bottom, and the second tube is used to pass a cleaning agent or a disinfectant into the second buffer; A fourth row of openings is provided at the bottom of the second buffer.
[0012] In combination with the first aspect, in a possible implementation, the influenza vaccine semi-finished product sterilization system also includes a power assembly, and the power assembly includes a first liquid pump and a second liquid pump, the first liquid pump is arranged between the liquid inlet pipe and the first filter assembly, and the second liquid pump is arranged between the second filter assembly and the first filter assembly.
[0013] In conjunction with the first aspect, in one possible implementation, the monitoring system includes: a first pressure detector, disposed on the top of the first filter system, the first pressure detector being used to detect the hydraulic pressure in the first filter system; a second pressure detector, disposed on the top of the second filter system, the second pressure detector being used to detect the hydraulic pressure in the second filter system; an audible and visual alarm, mounted on the outer wall of the sterile box; and A processing unit is arranged on a side wall of the sterile box, and the processing unit is communicatively connected with the first pressure detector, the second pressure detector and the sound and light alarm respectively.
[0014] Compared with the prior art, the influenza vaccine semi-finished product sterilization system provided by the present application is a system in which the semi-finished liquid medicine enters the sterile box through the liquid inlet pipe, first flows through the first filter component, and uses the first filter element to preliminarily filter out larger particle impurities. Subsequently, the preliminarily filtered liquid medicine enters the second filter component, and the second filter element with higher filtration accuracy further filters tiny impurities, and finally flows out of the sterile box through the liquid outlet pipe, completing the sterilization process. The monitoring system monitors the integrity of the first filter element and the second filter element in real time. By adopting a two-stage filter component and the filtration accuracy of the first filter element is lower than that of the second filter element, graded filtration of the influenza vaccine semi-finished product is achieved, which can more efficiently and accurately remove impurities of different particle sizes and improve the filtration effect. At the same time, the setting of the monitoring system can promptly detect the integrity problems of the filter element, ensure the stability and reliability of the filtration process, and avoid impurities entering the filtrate due to damage to the filter element, thereby improving the quality of the vaccine.
[0015] In a second aspect, a process for sterilizing semi-finished influenza vaccines is provided, which is implemented based on a system for sterilizing semi-finished influenza vaccines according to any one of the possible implementations described above, and is characterized in that it includes the following steps: S1. Using a monitoring system, perform integrity detection on a first filter element in the first filter assembly and a second filter element in the second filter assembly; S2. Clean and disinfect the liquid inlet pipe, the first filter assembly, the second filter assembly, and the liquid outlet pipe; S3. Sterilize the sterilization box at high temperature for a duration of not less than 1 hour; S4, introducing the semi-finished drug liquid from the inlet of the liquid inlet pipe, allowing the semi-finished drug liquid to pass through the first filter assembly and the second filter assembly in sequence, and finally discharge from the sterile box through the liquid outlet pipe to complete sterilization; S5. Repeat steps S1 to S4 until all semi-finished liquid medicines are processed.
[0016] The influenza vaccine semi-finished product sterilization process provided in this application, compared with the prior art, is that the semi-finished liquid medicine enters the sterile box through the liquid inlet pipe, first flows through the first filter component, and uses the first filter element to preliminarily filter out larger particle impurities. Subsequently, the preliminarily filtered liquid medicine enters the second filter component, and the second filter element with higher filtration accuracy further filters out tiny impurities, and finally flows out of the sterile box through the liquid outlet pipe, completing the sterilization process. The monitoring system monitors the integrity of the first filter element and the second filter element in real time. The use of a two-stage filter component and the filtration accuracy of the first filter element is lower than that of the second filter element achieves graded filtration of the influenza vaccine semi-finished product, which can more efficiently and accurately remove impurities of different particle sizes and improve the filtration effect. At the same time, the setting of the monitoring system can promptly detect problems with the integrity of the filter element, ensure the stability and reliability of the filtration process, and prevent impurities from entering the filtrate due to filter element damage, thereby improving the quality of the vaccine. The sterilization process steps are clear. By performing an integrity test on the filter element before each operation, problematic filter elements can be promptly discovered and replaced to ensure the filtration effect. Cleaning and disinfecting the pipes and components, as well as high-temperature sterilization of the sterile chamber 1, effectively reduces microorganisms and impurities within the system, providing a clean environment for sterilizing the vaccine semi-finished product. This entire process cycle ensures continuous, stable, and efficient sterilization of the influenza vaccine semi-finished product, improving vaccine quality and production efficiency. BRIEF DESCRIPTION OF THE DRAWINGS
[0017] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative labor.
[0018] Figure 1 This is a schematic diagram of the main structure of a system for sterilizing semi-finished influenza vaccines provided in one embodiment of the present application; Figure 2 This is a rear view of a semi-finished influenza vaccine sterilization system used in one embodiment of the present application; Figure 3 This is a schematic diagram of the assembly of the first filter assembly and the second filter assembly used in one embodiment of the present application; Figure 4 This is a rear view of the first filter assembly and the second filter assembly used in one embodiment of the present application; Figure 5 A front view of a first filter assembly and a second filter assembly used in another embodiment of the present application; Figure 6 This is a structural front view of a semi-finished influenza vaccine sterilization system provided by another embodiment of the present application, wherein the sterile box is for semi-processing; Figure 7 for Figure 6 A schematic structural diagram of the first filter assembly and the second filter assembly used in the embodiment; Figure 8 This is a structural front view of a semi-finished influenza vaccine sterilization system provided in another embodiment of the present application.
[0019] Description of reference numerals: 1. Sterile box; 11. Liquid inlet pipe; 12. Liquid outlet pipe; 13. Steam pipe; 14. First medium pipe; 15. Second medium pipe; 16. Universal wheel; 2. First filter assembly; 21. First filter; 211. First exhaust port; 22. First filter element; 23. First buffer; 231. First pipe; 232. First spray ball; 233. Second exhaust port; 24. First connecting pipe; 241. First exhaust port; 3. Second filter assembly; 31. Second filter; 311. Second exhaust port; 32. Second filter element; 33. Second buffer; 331. Second pipe; 332. Second spray ball; 333. Fourth exhaust port; 34. Second connecting pipe; 341. Third exhaust port; 4. Monitoring system; 41. First pressure detector; 42. Second pressure detector; 43. Sound and light alarm; 44. Processing unit; 5. Power assembly; 51. First liquid pump; 52. Second liquid pump. DETAILED DESCRIPTION
[0020] In order to make the technical problems, technical solutions and beneficial effects to be solved by this application more clearly understood, this application is further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain this application and are not intended to limit this application.
[0021] The following will be combined with the drawings in the embodiments of the present application to clearly and completely describe the technical solutions in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. The following description of at least one exemplary embodiment is actually only illustrative and is in no way intended to limit the present application and its application or use. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of this application.
[0022] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit the exemplary embodiments according to the present application. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprise" and / or "include" are used in this specification, they indicate the presence of features, steps, operations, devices, components and / or combinations thereof.
[0023] It should also be noted that, unless otherwise expressly specified or limited, terms such as "installed," "connected," "connect," "fixed," and "set" should be understood broadly. For example, they may refer to fixed or detachable connections, or integration; mechanical or electrical connections; direct or indirect connections through an intermediate medium; and may encompass internal communication between two components or interaction between two components. Those skilled in the art will understand the specific meanings of these terms in the present invention based on specific circumstances.
[0024] Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of technical features being referenced. Thus, a feature specified as "first" or "second" may explicitly or implicitly include one or more of such features. Furthermore, "plurality" and "several" mean two or more, unless otherwise specifically defined.
[0025] Please also refer to Figures 1 to 8, the influenza vaccine semi-finished product sterilization system provided by the present application is now described. The influenza vaccine semi-finished product sterilization system includes a sterile box 1, a first filter component 2, a second filter component 3 and a monitoring system 4. The sterile box 1 has a liquid inlet pipe 11 on one side and a liquid outlet pipe 12 on the other side; the first filter component 2 is arranged in the sterile box 1, the liquid inlet of the first filter component 2 is connected to the outlet of the liquid inlet pipe 11, and the first filter component 2 has a first filter element 22; the second filter component 3 is arranged in the sterile box 1, the liquid inlet of the second filter component 3 is connected to the liquid outlet of the first filter component 2, the liquid outlet of the second filter component 3 is connected to the inlet of the liquid outlet pipe 12, the second filter component 3 has a second filter element 32, and the filtration accuracy of the first filter element 22 is lower than the filtration accuracy of the second filter element 32; the monitoring system 4 is arranged in the sterile box 1, and the monitoring system 4 is used to monitor the integrity of the first filter element 22 and the second filter element 32.
[0026] It should be noted that the interior of the sterile box 1 is in a sealed sterile state, ensuring that the first filter component 2 and the second filter component 3 are in a sterile environment, thereby preventing the semi-finished drug liquid from being contaminated by bacteria in the air.
[0027] It should be noted that the inlet of the liquid inlet pipe 11 and the outlet of the liquid outlet pipe 12 are respectively connected to the outside world, the inlet of the liquid inlet pipe is connected to the outlet of the semi-finished product liquid pipe, and the outlet of the liquid outlet pipe 12 is connected to the inlet of the packaging process.
[0028] In practice, sterile box 1 is equipped with an air filter to filter the air entering the box. Air generally enters from the top of the sterile box 1 and exits from the bottom, forming a downward, unidirectional airflow that removes any microorganisms or particles generated by the operator. A UV lamp inside sterile box 1 performs ultraviolet disinfection, disinfecting the outer surfaces of the first and second filter assemblies 2 and 3 within the box. During operation, sterile box 1 is sealed, completely isolating itself from the outside, bacteria-laden air.
[0029] As an embodiment of operating parts in the sterile box 1 , the sterile box 1 is provided with glove holes connected to sterile gloves, and the gloves are used to adjust the internal system to ensure the sterility of the interior of the sterile box 1 .
[0030] It should be noted that the pore size of the first filter element 22 is 0.4-0.5 μm, and the pore size of the second filter element 32 is 0.2-0.3 μm. Preferably, the pore size of the first filter element 22 is 0.45 μm, and the pore size of the second filter element 32 is 0.22 μm.
[0031] In this embodiment, the semi-finished liquid medicine enters the sterile chamber 1 through the liquid inlet pipe 11 and first flows through the first filter assembly 2, where the first filter element 22 initially filters out larger particles of impurities. The pre-filtered liquid medicine then enters the second filter assembly 3, where the second filter element 32, with higher filtration accuracy, further filters out fine impurities. The liquid medicine finally flows out of the sterile chamber 1 through the liquid outlet pipe 12, completing the sterilization process. The monitoring system 4 monitors the integrity of the first and second filter elements 22, 32 in real time.
[0032] Compared to existing technologies, the influenza vaccine semi-finished product sterilization system provided in this embodiment utilizes a two-stage filtration assembly, with the first filter element 22 having a lower filtration accuracy than the second filter element 32. This achieves graded filtration of the influenza vaccine semi-finished product, more efficiently and accurately removing impurities and microorganisms of varying particle sizes, thereby improving filtration effectiveness. Furthermore, the provision of a monitoring system 4 allows for timely detection of filter integrity issues, ensuring the stability and reliability of the filtration process and preventing impurities from entering the filtrate due to filter damage, thereby improving vaccine quality.
[0033] In some embodiments, see Figure 8 The bottom of the sterile box 1 is provided with universal wheels 16, and employees can push the entire system to move. When the sterile box 1 needs to be sterilized, the sterile box 1 is pushed to the designated position and docked with the steam equipment, which increases the convenience of equipment use and facilitates equipment maintenance, cleaning and sterilization operations.
[0034] In some embodiments, the first filter assembly 2 and the second filter assembly 3 are installed as follows: Figure 1 and Figure 3 As shown, it extends along the length direction of the sterile box 1; it can also be as shown Figure 6 and Figure 7 The design method can greatly utilize the internal space of the sterile box 1.
[0035] In some embodiments, see Figure 1 and Figure 3The inlet of the liquid inlet pipe 11 is connected to the drug pipe, through which the semi-finished vaccine solution flows. The liquid inlet pipe 11 is also connected to a steam pipe 13 and a first medium pipe 14, respectively, for introducing a cleaning agent or disinfectant. The outlet of the liquid outlet pipe 12 is also connected to a second medium pipe 15, for discharging the cleaning agent or disinfectant. The liquid inlet pipe 11 is connected to the drug pipe for inputting the semi-finished drug solution, while also connecting to the steam pipe 13 and the first medium pipe 14. The outlet of the liquid outlet pipe 12 is connected to the second medium pipe 15 for discharging the cleaning agent or disinfectant. This design allows the pipeline to be cleaned and sterilized with the cleaning agent or disinfectant before and after filtration, effectively preventing residual impurities and microorganisms in the pipeline from contaminating the semi-finished vaccine solution, ensuring the cleanliness of the entire sterilization system and further improving vaccine quality. The steam pipe 13 allows for high-temperature sterilization, while the first and second medium pipes 14 and 15 cooperate to pass the cleaning agent or disinfectant into the first and second filtration systems for cleaning and sterilization, ensuring the cleanliness of the filtration systems when the semi-finished drug solution is introduced, thereby ensuring the quality of the drug solution.
[0036] It should be noted that the cleaning agent is introduced using CIP (Cleaning in Place) technology. CIP stands for Cleaning in Place (CIP) and can remove both visible and invisible residues within pipes. Through a pre-set process (e.g., pipes and nozzles), a cleaning fluid (water, acid, alkali, disinfectant, etc.) is pumped into the equipment, automatically completing flushing, soaking, and circulation steps to remove residues (e.g., drug residue, protein, fat, etc.) on the equipment's internal surfaces, ultimately achieving cleanliness standards. In this example, water was used as the cleaning agent, and 0.1N sodium hydroxide as the disinfectant.
[0037] The disinfectant is introduced using SIP, which stands for online sterilization. The cleaning liquid (water, acid, alkali, disinfectant, etc.) is pumped into the equipment through a preset program (such as pipes, nozzles), automatically completing the steps of flushing, soaking, and circulation to remove residues on the inner surface of the equipment (such as liquid medicine residue, protein, fat, etc.), and ultimately meet the cleaning standards.
[0038] Saturated steam sterilization is usually used (121°C, 103kPa pressure for 30 minutes, or 134°C for 18 minutes). The steam must be dry and free of condensed water (to avoid localized under-temperature). It should be noted that CIP is performed first and then SIP, that is, cleaning agent is introduced first and then disinfectant is introduced for disinfection.
[0039] In some embodiments, see Figure 1 、 Figures 3 to 5The first filtration system further includes a first filter 21, a first buffer 23, and a first connecting pipe 24. The first filter 21 is installed in the sterile box 1, with the bottom inlet of the first filter 21 communicating with the liquid inlet pipe 11. The first filter element 22 is installed in the first filter 21, and a first exhaust port 211 is provided at the top of the first filter 21. The first buffer 23 is installed in the sterile box 1, with the bottom outlet of the first buffer 23 communicating with the second filtration system. The first connecting pipe 24 has two ends that respectively communicate with the bottom inlet of the first buffer 23 and the bottom outlet of the first filter 21. The end of the first connecting pipe 24 near the first filter 21 is connected to a first exhaust port 241.
[0040] It should be noted that the first buffer 23 can temporarily store the semi-finished liquid medicine to avoid the rapid flow of the semi-finished liquid medicine causing internal bubbles. The semi-finished liquid medicine is buffered in the buffer to reduce the generation of bubbles and improve the final quality of the liquid medicine.
[0041] In specific implementation, a support frame is provided at the bottom of the first buffer 23 and the first filter 21 , and the bottom of the support frame contacts the bottom of the sterile box 1 to stably fix the first buffer 23 and the first filter 21 in the sterile box 1 .
[0042] The first filtration system of this embodiment has a simple structure. The bottom inlet of the first filter 21 is connected to the liquid inlet pipe 11, and a first exhaust port 211 is provided at the top to facilitate the discharge of gases generated during the filtration process, preventing air blockage from affecting the filtration efficiency. The first buffer 23 can buffer the liquid medicine after preliminary filtration, ensuring a smoother flow of the liquid medicine. The first connecting pipe 24 connects the first filter 21 and the first buffer 23, and a first exhaust port 241 is provided near one end of the first filter 21 to facilitate the discharge of impurities that may have accumulated at the bottom of the filter, maintaining the normal operation of the first filter assembly 2 and ensuring the overall filtration effect.
[0043] In some embodiments, see Figure 3 and Figure 5 The first buffer 23 is equipped with a first tube 231 at the top, extending downward into the first buffer 23. A first spray ball 232 is located at the bottom. The first tube 231 is used to introduce cleaning agent or disinfectant into the first buffer 23. A second outlet 233 is provided at the bottom of the first buffer 23. The first tube 231 at the top and the first spray ball 232 at the bottom of the first buffer 23 allow the cleaning and sterilization media to evenly clean and disinfect the interior of the first buffer 23 during CIP / SIP operation, ensuring that no impurities or microorganisms remain within the first buffer 23. The second outlet 233 at the bottom of the first buffer 23 facilitates the discharge of cleaning waste liquid, further ensuring the cleanliness of the first buffer 23 and providing a good environment for subsequent filtration operations.
[0044] During specific implementation, the first spray ball 232 is placed in the inner cavity of the first buffer 23. The first spray ball 232 can convert the liquid column of the cleaning agent or disinfectant into multiple streams of water at different angles. When the high-pressure cleaning liquid passes through the spray ball, it will be ejected from these holes at high speed to form a rotating or fan-shaped jet of water. The impact force and coverage of the water flow are used to evenly flush every area of the inner surface of the equipment. In conjunction with CIP, there is no need to disassemble the equipment, thus avoiding external contamination that may be caused by manual opening of the cover for cleaning.
[0045] In some embodiments, see Figure 4 The first filter 21 includes a housing and a mounting bracket. The housing is installed in the sterile box 1, with a first exhaust port 211 defined at the top. The mounting bracket is mounted within the housing, forming a vertically extending filter channel within the mounting bracket. The central axis of the filter channel overlaps with the central axis of the housing. The first filter element 22 is installed within the filter channel, the bottom end of which is connected to the first connecting pipe 24. The outlet of the liquid inlet pipe 11 is connected to the bottom of the housing.
[0046] It should be noted that the first exhaust port 211 is equipped with an air filter to avoid pipeline pollution.
[0047] During specific implementation, the medicine liquid inlet and the medicine liquid outlet on the first filter 21 are both at the bottom and are not connected to each other. After the semi-finished medicine liquid enters the first filter 21 from the liquid inlet pipe 11, it can only continue to accumulate until the liquid level of the medicine liquid is higher than the top of the filter channel. The medicine liquid flows downward from the top of the filter channel, and impurities are screened out under the filtering action of the first filter element 22. The medicine liquid flows from the medicine liquid outlet to the first connecting pipe 24.
[0048] In this embodiment, the housing of the first filter 21 is installed within the sterile chamber 1 and fixedly mounted therein to form a vertically extending filtration channel. The first filter element 22 is mounted within the filtration channel, and the bottom end of the filtration channel is connected to the first connecting pipe 24. The outlet of the liquid inlet pipe 11 is connected to the bottom of the housing. This structural design allows the medicinal liquid to be evenly filtered through the first filter element 22, improving the uniformity and stability of the filtration, reducing filtration blind spots, and enhancing the filtration effect of the first filter assembly 2.
[0049] In some embodiments, see Figure 1 and Figure 3The second filtering system also includes a second filter 31, a second buffer 33 and a second connecting pipe 34; the second filter 31 is installed in the sterile box 1, the bottom inlet of the second filter 31 is connected to the outlet of the first filter assembly 2, the second filter element 32 is installed in the second filter 31, and the top of the second filter 31 is provided with a second exhaust port 311; the second buffer 33 is installed in the sterile box 1, and the bottom outlet of the second buffer 33 is connected to the inlet of the liquid outlet pipe 12; the two ends of the second connecting pipe 34 are respectively connected to the bottom inlet of the second buffer 33 and the bottom outlet of the second filter 31, and the two ends of the second connecting pipe 34 close to the second filter 31 are connected to the third exhaust port 341.
[0050] It should be noted that the second buffer 33 and the first buffer 23 have the same function.
[0051] It should be noted that the second exhaust port 311 is equipped with an air filter to avoid pipeline pollution.
[0052] In this embodiment, the bottom inlet of the second filter 31 is connected to the outlet of the first filter assembly 2, and a second exhaust port 311 is provided at the top to discharge the gases generated by the filtration. The second buffer 33 buffers the liquid medicine after being filtered by the first filter assembly 2 and the second filter 31, ensuring a more stable flow of the liquid medicine. The second connecting pipe 34 connects the second filter 31 and the second buffer 33, and a third exhaust port 341 is provided near one end of the second filter 31 to facilitate the discharge of impurities accumulated at the bottom of the second filter 31, ensuring the normal operation of the second filter assembly 3, thereby improving the overall sterilization system's ability to filter out small impurities.
[0053] In some embodiments, see Figure 1 、 Figures 3 to 5 A second tube 331 is provided at the top of the second buffer 33, the bottom of the second tube 331 extends into the second buffer 33, and a second spray ball 332 is provided at the bottom. The second tube 331 is used to introduce cleaning agent or disinfectant into the second buffer 33; a fourth outlet 333 is opened at the bottom of the second buffer 33.
[0054] It should be noted that the structure of the second filter 31 is the same as that of the first filter 21 , and will not be described in detail here.
[0055] In this embodiment, the second tube 331 at the top and the second spray ball 332 at the bottom of the second buffer 33 evenly clean and disinfect the interior of the second buffer 33 during CIP / SIP operation, preventing microbial growth and residual impurities. A fourth drain port 333 at the bottom of the second buffer 33 facilitates the discharge of cleaning waste liquid, ensuring the cleanliness of the second buffer 33 and providing a clean temporary storage space for the sterilized drug solution, thereby ensuring the quality of the semi-finished vaccine product.
[0056] In a specific implementation, the second spray ball 332 and the first spray ball 232 have the same structure and play the same role.
[0057] In some embodiments, see Figure 1 and Figure 3 The influenza vaccine semi-finished product sterilization system also includes a power assembly 5, which includes a first liquid pump 51 and a second liquid pump 52. The first liquid pump 51 is located between the liquid inlet pipe 11 and the first filter assembly 2, and the second liquid pump 52 is located between the second filter assembly 3 and the first filter assembly 2. The first liquid pump 51 and the second liquid pump 52 are arranged to provide power for the flow of the liquid medicine within the system, ensuring that the liquid medicine can pass through the first filter assembly 2 and the second filter assembly 3 in sequence at an appropriate flow rate, avoiding the impact of slow flow rate on production efficiency or excessive flow rate on inadequate filtration, thereby optimizing the entire sterilization process.
[0058] During specific implementation, the first liquid pump 51 and the second liquid pump 52 have the same structure. The first liquid pump 51 pumps the semi-finished liquid medicine from the liquid inlet pipe 11 to the first filter 21, and the second liquid pump 52 pumps the semi-finished liquid medicine from the first buffer 23 to the second filter 31, giving power to the semi-finished liquid medicine to ensure that the semi-finished liquid medicine can be sterilized and filtered smoothly.
[0059] In some embodiments, see Figure 2 and Figure 5 The monitoring system 4 includes a first pressure detector 41, a second pressure detector 42, an audible and visual alarm 43, and a processing unit 44. The first pressure detector 41 is located on the top of the first filter system and is used to detect the hydraulic pressure in the first filter system; the second pressure detector 42 is located on the top of the second filter system and is used to detect the hydraulic pressure in the second filter system; the audible and visual alarm 43 is installed on the outer wall of the sterile box 1; and the processing unit 44 is located on the side wall of the sterile box 1 and is communicatively connected to the first pressure detector 41, the second pressure detector 42, and the audible and visual alarm 43, respectively.
[0060] During specific implementation, the sound and light alarm 43 adopts an intelligent network alarm light.
[0061] In specific implementation, the first pressure detector 41 includes two first pressure gauges 5, which are respectively installed on the upstream and downstream pipelines of the first filter 21; the second pressure detector 42 includes two second pressure gauges 5, which are respectively installed on the upstream and downstream pipelines of the second filter 31.
[0062] The monitoring system 4 provided in this embodiment uses a pressure differential comparison method. Taking the inspection of the first filter element 22 as an example, the upstream and downstream pipes of the first filter 21 are sealed. Liquid is allowed to flow through the first filter 21. The pressure source is activated. After a period of quiescence, P1 (upstream pressure) and P2 (downstream pressure) are recorded. The pressure differential P is calculated as P = P1 - P2. If P is lower than the standard pressure differential of the first filter element 22, it indicates that the first filter element 22 is incomplete or damaged. If P is higher than the standard pressure differential of the first filter element 22, it indicates that the first filter element 22 is clogged. If P is lower than the standard pressure differential of the first filter element 22, which is close to the standard, it indicates that the first filter element 22 is intact.
[0063] The pressure detector in the monitoring system 4 provided in this embodiment is located at the top of the first filter 21 and is used to detect the pressure within the first filter 21. If the first filter element 22 exhibits integrity issues, such as damage, the pressure within the filter will change. Upon detecting the abnormal pressure, the pressure detector transmits a signal to the processing unit 44. The processing unit 44 then controls the audible and visual alarm 43 to sound an alarm, alerting personnel to promptly address the issue. This monitoring system 4 monitors the status of the first filter element 22 in real time, ensuring the proper operation of the first filter assembly 2 and, consequently, the stability of the entire sterilization system and the quality of the vaccine.
[0064] As another embodiment of the detection system, the detection system is provided in two groups, each comprising a compressed air storage tank and a graduated cylinder inverted in a water container and filled with water. The exhaust port of the compressed air storage tank is connected to the inlet of the first filter 21 / second filter 31, and the air inlet of the graduated cylinder is connected to the outlet of the first filter 21 / second filter 31. The graduated cylinder is filled with water and inverted in the water-filled container. The first filter 21 / second filter 31 is filled with purified water. Gas is discharged from the compressed air storage tank, passes through the first filter 21 / second filter 31 in sequence, and finally enters the graduated cylinder. If the amount of gas collected in the graduated cylinder is higher than the qualified diffusion flow value of the first filter element 22 / second filter element 32, it indicates that the first filter element 22 / second filter element 32 is incomplete. If the amount of gas collected in the graduated cylinder is lower than or equal to the qualified diffusion flow value of the first filter element 22 / second filter element 32, it indicates that the first filter element 22 / second filter element 32 is intact.
[0065] During specific implementation, the first exhaust port 211, the second exhaust port 233, the first exhaust port 241, the second exhaust port 311, the fourth exhaust port 333 and the third exhaust port 341 are respectively installed with temperature probes, and the temperature probes are respectively communicated with the processing units to facilitate technicians to intuitively understand the temperature of each outlet.
[0066] Based on the same inventive concept, the present application also provides a sterilization process for influenza vaccine semi-finished products, which is implemented based on the influenza vaccine semi-finished product sterilization system as any one of the above embodiments, and includes the following steps: S1, using the monitoring system 4 to detect the integrity of the first filter element 22 in the first filter component 2 and the second filter element 32 in the second filter component 3; S2, cleaning and disinfecting the liquid inlet pipe 11, the first filter component 2, the second filter component 3 and the liquid outlet pipe 12; S3, performing high-temperature sterilization on the sterile box 1 for a duration of not less than 1 hour; S4, introducing the semi-finished liquid medicine from the inlet of the liquid inlet pipe 11, allowing the semi-finished liquid medicine to pass through the first filter component 2 and the second filter component 3 in sequence, and finally being discharged from the sterile box 1 from the liquid outlet pipe 12 to complete sterilization; S5, repeating steps S1 to S4 until the semi-finished liquid medicine is completely processed.
[0067] In this embodiment, before each sterilization operation, the monitoring system 4 is used to perform an integrity check on the first filter element 22 and the second filter element 32 to ensure that the filter elements are not damaged. Then, through the connecting structure of the liquid inlet pipe 11, the first filter component 2, the second filter component 3 and the liquid outlet pipe 12, CIP / SIP is introduced to clean and disinfect each part to remove residual impurities and microorganisms. Then, the sterile box 1 is sterilized to create a closed sterile environment. Subsequently, the semi-finished drug liquid is introduced from the liquid inlet pipe 11, and the drug liquid passes through the first filter component 2 and the second filter component 3 in turn. Impurities are gradually removed by filter elements of different precisions, and finally discharged from the sterile box 1 from the liquid outlet pipe 12, completing a sterilization operation. The above steps are repeated in this way.
[0068] Compared to existing technologies, the influenza vaccine semi-finished product sterilization process provided in this embodiment features clear sterilization steps. By performing filter integrity testing before each operation, problematic filter elements can be promptly identified and replaced, ensuring effective filtration. Cleaning and disinfecting the pipes and components, as well as high-temperature sterilization of the sterile chamber 1, effectively reduces microorganisms and impurities within the system, providing a clean environment for sterilization of the vaccine semi-finished product. The cyclic operation of the entire process ensures continuous, stable, and efficient sterilization of the influenza vaccine semi-finished product, improving vaccine quality and production efficiency.
[0069] The following is a specific embodiment of this application: Sterile filtration operation of semi-finished liquid medicine: Step 1: Check the integrity of the first filter element 22 and the second filter element 32; Step 2: Start the cleaning and disinfection program. Open the first medium pipe 14, the first pipe 231, and the second pipe 331, and introduce a cleaning agent or disinfectant into the pipes respectively. The cleaning agent is water for injection and the disinfectant is 0.1N sodium hydroxide. Step 3: After the cleaning agent cleaning and disinfection agent disinfection are completed, close the first medium pipe 14, the first pipe 231 and the second pipe 331, open the second medium pipe 15, drain the liquid, and complete the cleaning and disinfection; Step 4: Start the sterilization process, pass high-temperature steam from the steam pipe 13 to the first filter assembly 2 and the second filter assembly 3, open the first exhaust port 211 and the second exhaust port 311, the liquid outlet pipe 12, the first exhaust port 241, the third exhaust port 341, the second exhaust port 233, and the fourth exhaust port 333; the sterilization time is controlled at 60 minutes and the temperature is controlled at 120°C; Step 5: sterilize the sterile box and close the opening opened in step 4; Step 6: Start the filtration process and flow the semi-finished liquid medicine through the liquid inlet pipe 11, the first filter 21, the first buffer 23, the second filter 31, the second buffer 33 and the liquid outlet pipe 12 in this order. The end of the liquid outlet pipe 12 is connected to the inlet of the sub-packaging line, and the filtered semi-finished liquid medicine is packaged. Step seven, repeat steps one to five to complete the filtration of the semi-finished liquid medicine.
[0070] The above description is only a preferred embodiment of the present application and is not intended to limit the present application. Any modifications, equivalent replacements and improvements made within the spirit and principles of the present application should be included in the scope of protection of the present application.
Claims
1. A semi-finished influenza vaccine sterilization system, characterized in that: include: A sterile box having a liquid inlet pipe on one side and a liquid outlet pipe on the other side; A first filter assembly is disposed in the sterile box, wherein the liquid inlet of the first filter assembly is connected to the outlet of the liquid inlet pipe, and the first filter assembly has a first filter element; a second filter assembly disposed in the sterile box, wherein the liquid inlet of the second filter assembly is connected to the liquid outlet of the first filter assembly, and the liquid outlet of the second filter assembly is connected to the inlet of the liquid outlet pipe, and the second filter assembly has a second filter element, and the filtering accuracy of the first filter element is lower than the filtering accuracy of the second filter element; as well as A monitoring system is provided in the sterile box, and the monitoring system is used to monitor the integrity of the first filter element and the second filter element.
2. The influenza vaccine semi-finished product sterilization system according to claim 1, characterized in that: The inlet of the liquid inlet pipe is connected to the medicine pipe, and the semi-finished medicine liquid flows in the medicine pipe; the liquid inlet pipe is also connected to the steam pipe and the first medium pipe respectively, and the first medium pipe is used to pass the cleaning agent or disinfectant; The outlet of the liquid outlet pipe is also connected to a second medium pipe, and the second medium pipe is used to discharge cleaning agent or disinfectant.
3. The influenza vaccine semi-finished product sterilization system according to claim 1, characterized in that: The first filtration system further comprises: a first filter installed in the sterile box, wherein the bottom inlet of the first filter is connected to the liquid inlet pipe, the first filter element is installed in the first filter, and the top of the first filter is provided with a first exhaust port; A first buffer is installed in the sterile box, and a bottom outlet of the first buffer is connected to the second filtering system; and The first communicating pipe has two ends respectively connected to the bottom inlet of the first buffer and the bottom outlet of the first filter. One end of the first communicating pipe close to the first filter is connected to the first discharge port.
4. The influenza vaccine semi-finished product sterilization system according to claim 3, characterized in that: A first tube is provided on the top of the first buffer, extending downward into the first buffer, and a first spray ball is provided at the bottom. The first tube is used to introduce cleaning agent or disinfectant into the first buffer; a second discharge port is provided at the bottom of the first buffer.
5. The influenza vaccine semi-finished product sterilization system according to claim 3, characterized in that: The first filter comprises: a shell, installed in the sterile box, the top of the shell being provided with the first exhaust port; and A fixing frame is arranged inside the shell, and a vertically extending filter channel is formed inside the fixing frame. The central axis of the filter channel overlaps with the central axis of the shell. The first filter element is installed in the filter channel. The bottom end of the filter channel is connected to the first connecting pipe, and the outlet of the liquid inlet pipe is connected to the bottom of the shell.
6. The influenza vaccine semi-finished product sterilization system according to claim 1, characterized in that: The second filtration system further comprises: a second filter installed in the sterile box, wherein the bottom inlet of the second filter is connected to the outlet of the first filter assembly, the second filter element is installed in the second filter, and the top of the second filter is provided with a second exhaust port; A second buffer is installed in the sterile box, and a bottom outlet of the second buffer is connected to the inlet of the liquid outlet pipe; and The second communicating pipe has two ends respectively connected to the bottom inlet of the second buffer and the bottom outlet of the second filter. The two ends of the second communicating pipe close to the second filter are connected to the third outlet.
7. The influenza vaccine semi-finished product sterilization system according to claim 6, characterized in that: A second pipe is provided on the top of the second buffer, the bottom of the second pipe extends into the second buffer, and a second spray ball is provided at the bottom, and the second pipe is used to pass a cleaning agent or a disinfectant into the second buffer; A fourth row of openings is formed at the bottom of the second buffer.
8. The influenza vaccine semi-finished product sterilization system according to claim 1, characterized in that: The influenza vaccine semi-finished product sterilization system also includes a power component, which includes a first liquid pump and a second liquid pump. The first liquid pump is arranged between the liquid inlet pipe and the first filter component, and the second liquid pump is arranged between the second filter component and the first filter component.
9. The influenza vaccine semi-finished product sterilization system according to claim 1, characterized in that: The monitoring system comprises: a first pressure detector, disposed on the top of the first filter system, the first pressure detector being used to detect the hydraulic pressure in the first filter system; a second pressure detector, disposed on the top of the second filter system, the second pressure detector being used to detect the hydraulic pressure in the second filter system; an audible and visual alarm, mounted on the outer wall of the sterile box; and A processing unit is arranged on a side wall of the sterile box, and the processing unit is communicatively connected with the first pressure detector, the second pressure detector and the sound and light alarm respectively.
10. A process for sterilizing semi-finished influenza vaccine products, implemented based on the semi-finished influenza vaccine product sterilization system according to any one of claims 1 to 9, characterized in that: The following steps are involved: S1. Using a monitoring system, perform integrity detection on a first filter element in the first filter assembly and a second filter element in the second filter assembly; S2. Clean and disinfect the liquid inlet pipe, the first filter assembly, the second filter assembly, and the liquid outlet pipe; S3. Sterilize the sterilization box at high temperature for a duration of not less than 1 hour; S4, introducing the semi-finished drug liquid from the inlet of the liquid inlet pipe, allowing the semi-finished drug liquid to pass through the first filter assembly and the second filter assembly in sequence, and finally discharge from the sterile box through the liquid outlet pipe to complete sterilization; S5. Repeat steps S1 to S4 until all semi-finished liquid medicines are processed.