An inactivation hydrolysis device and inactivation method

Abstract

The application relates to the field of biotechnology, and particularly relates to an inactivation hydrolysis device which comprises an internally hollow and closed liquid storage bag made of a flexible film material, the liquid storage bag is provided with a liquid inlet and a liquid outlet, the liquid inlet and the liquid outlet are both connected with sterile quick connectors, and a heating assembly for water bath heating of the liquid storage bag is arranged outside the liquid storage bag; the application also relates to an inactivation method of the inactivation hydrolysis device, which comprises the following steps: adding a material liquid into the liquid storage bag; adding virus harvest liquid into the liquid storage bag, and washing the top with PBS solution, diluting virus inactivator beta-propiolactone into a concentration of 1:4000, adding the virus inactivator beta-propiolactone into the liquid storage bag, and stirring; raising the temperature in the liquid storage bag to 37 DEG C, and performing water bath heating, and adjusting the PH value of the material liquid in the liquid storage bag; after hydrolysis is completed, the material liquid is discharged from the liquid storage bag; the application has the effects of improving the reliability and safety in the inactivation hydrolysis process, and avoiding bacterial infection.

Description

Technical Field

[0001] This application relates to the field of biotechnology, and in particular to an inactivation hydrolysis device and inactivation method. Background Technology

[0002] The main vaccines used domestically and internationally include live attenuated vaccines and inactivated vaccines. Inactivated vaccines are favored due to their simple production process, safety, ease of use, ease of storage, ability to stimulate high-titer antibody production in animals, and significant protective effects. Therefore, developing high-quality and highly effective inactivated vaccines is an effective measure for controlling various viral infections.

[0003] Currently, both inactivated vaccines and monoclonal antibodies on the market require a virus inactivation step, followed by hydrolysis and neutralization, before they can enter the trial use stage. However, there is currently no readily available and effective inactivation and hydrolysis device. Most existing methods use heating and stirring for inactivation, which requires multiple manual operations. During these operations, the inactivated vaccines and monoclonal antibodies are exposed to the outdoor environment multiple times, which can easily lead to their inactivation and failure. Furthermore, the manual heating and stirring method for inactivation has poor repeatability, and the efficiency of virus inactivation and the degree of hydrolysis cannot be guaranteed. In addition, multiple exposure operations can easily cause bacterial contamination. Summary of the Invention

[0004] To improve the reliability and safety of the inactivation hydrolysis process and to minimize bacterial infection, this application provides an inactivation hydrolysis device and an inactivation method.

[0005] This application provides an inactivation hydrolysis device and inactivation method, which adopts the following technical solution:

[0006] In a first aspect, this application provides an inactivation hydrolysis device, which adopts the following technical solution:

[0007] An inactivation hydrolysis device includes a hollow and sealed liquid storage bag made of a transparent flexible membrane material. The liquid storage bag has an inlet and an outlet, both of which are connected to sterile quick connectors. A heating component for water bath heating of the liquid storage bag is provided on the outside of the liquid storage bag.

[0008] By adopting the above technical solution, the entire inactivation and hydrolysis process is carried out inside the sealed storage bag, eliminating the need for frequent container replacements. This improves the reliability and safety of virus inactivation and hydrolysis, and the sealed structure of the storage bag minimizes the risk of bacterial infection.

[0009] Optionally, the heating assembly includes an outer jacket bag fitted over the liquid storage bag, forming a hollow water jacket between the outer jacket bag and the liquid storage bag, the sterile quick connector extending outward through the outer jacket bag, the outer jacket bag being provided with an inlet and an outlet, and a water temperature control system being connected between the inlet and outlet via a pipeline.

[0010] By adopting the above technical solution, the water temperature control system can control the temperature of the water inside the water jacket at any time, thereby quickly reaching the temperature range required in the inactivation and hydrolysis process, ensuring the reliability of virus inactivation and hydrolysis.

[0011] Optionally, a temperature probe and a pH probe are installed inside the liquid storage bag, and a controller is installed outside the outer jacket bag, the controller being electrically connected to the temperature probe and the pH probe.

[0012] By adopting the above technical solution, the controller can be connected to the water temperature control system. The temperature probe can monitor the temperature inside the water jacket in real time, and the water temperature can be adjusted according to actual needs, thereby controlling the temperature of the liquid inside the storage bag. The pH probe installed inside the storage bag can monitor the acidity or alkalinity of the liquid inside the storage bag in real time. When the acidity or alkalinity of the liquid exceeds or falls below the design requirements, the pH probe detects the signal and transmits it to the controller. The controller can then adjust the acidity or alkalinity of the liquid by supplying liquid into the storage bag through the inlet, or by introducing gas into the storage bag to adjust the pH value of the liquid.

[0013] Optionally, the water interlayer between the outer jacket bag and the liquid storage bag is provided with an inflatable skeleton.

[0014] By adopting the above technical solution, the inflatable frame can be supported between the outer jacket bag and the liquid storage bag, and ensure that the water in the water jacket can evenly wrap the liquid storage bag, thereby ensuring that the temperature rise or fall can be evenly controlled.

[0015] Optionally, the inactivation hydrolysis device further includes a swing bed reactor, on which the external jacket bag and the storage bag can be placed, and the swing bed reactor is connected to a controller.

[0016] By adopting the above technical solution, the set swing bed reactor can swing and mix the liquid in the storage bag and ensure uniform mixing, which greatly improves the reliability of virus inactivation and hydrolysis, reduces labor intensity, and avoids the need for staff to mix and stir. In addition, the swing bed reactor and controller can control the swing speed, which makes it easier and faster to mix the liquid inside the storage bag evenly.

[0017] Optionally, the liquid storage bag is connected to an air inlet valve and an air outlet valve, and a pressure gauge is connected to the air outlet valve.

[0018] By adopting the above technical solution, the exhaust valve can release the pressure inside the storage bag, eliminating positive pressure inside the storage bag and facilitating the filling of the storage bag with liquid through the inlet. When the pH value inside the storage bag exceeds the standard or falls below the normal value, gas can be added into the storage bag through the air inlet valve. After the inactivation and hydrolysis are completed, the air inlet valve is connected to sterile compressed air, and the air inlet valve is opened to gradually fill the storage bag with gas at a certain pressure, allowing the liquid inside the storage bag to be quickly discharged through the outlet. During the process of adding gas into the storage bag, the pressure inside the storage bag can be monitored in real time using a pressure gauge.

[0019] Optionally, the liquid storage bag is also provided with a sampling port, and a sterile quick connector is connected to the sampling port.

[0020] By adopting the above technical solution, the sampling port can extract the liquid material from the reaction process inside the storage bag and test it.

[0021] Optionally, a magnetic rotor is installed inside the liquid storage bag, the inactivation hydrolysis device includes a stainless steel tank, the outer jacket bag and the liquid storage bag are installed inside the stainless steel tank, and a magnetic stirrer that cooperates with the magnetic rotor is installed outside the stainless steel tank. The magnetic stirrer is connected to the controller.

[0022] By adopting the above technical solution, when the liquid volume inside the storage bag is large, the magnetic rotor can be driven to rotate under the action of the magnetic stirrer. The magnetic stirrer is connected to the controller, which can control the magnetic stirrer and the magnetic rotor, thereby controlling the stirring speed of the liquid inside the storage bag. It can also avoid the problem of dead corners during the stirring process to the greatest extent, making the stirring and mixing more uniform.

[0023] Secondly, this application provides a deactivation method for a deactivation hydrolysis device, which adopts the following technical solution:

[0024] A method for deactivating a hydrolysis device includes the following steps:

[0025] Feeding: The sterile quick connector on the inlet connects to the liquid supply source, allowing the liquid to enter the storage bag;

[0026] Inactivation: Add virus harvesting fluid to the inside of the storage bag, add PBS solution to the inside of the storage bag and perform top washing, dilute the virus extinguishing agent β-propiolactone to a concentration of 1:4000 and add it to the inside of the storage bag, then place the outer jacket bag and the storage bag on the swing bed reactor or stir with a magnetic stirrer. During the stirring process, the water temperature of the water jacket is controlled at 2-8℃ through the water temperature control system and inactivation is continued for 24 hours.

[0027] Hydrolysis: The water temperature inside the water jacket is raised to 37°C through the water temperature control system and heated continuously for 23 hours to completely hydrolyze the extinguishing agent. During the hydrolysis process, the value detected by the pH probe is continuously observed. Then, NaOH solution is added to the storage bag to adjust the pH value of the virus inactivation solution to reach the specified acidity or alkalinity.

[0028] Discharge: Remove the inactivated liquid after hydrolysis for the next process, and sterilize the used outer jacket bag and storage bag at high temperature before disposal.

[0029] In summary, this application includes at least one of the following beneficial technical effects:

[0030] 1. Using pre-sterilized disposable sterile storage bags, and the entire inactivation and hydrolysis process can be carried out in the bag without frequent container changes, greatly improves the reliability and safety of virus inactivation and hydrolysis, minimizes bacterial contamination, and reduces labor intensity and costs.

[0031] 2. The virus inactivation storage bag allows for full contact between the virus inactivating agent and the virus. Liquids under 20L can be placed on a swing bed reactor, where the swinging motion ensures contact. Storage bags between 20L and 100L have a built-in magnetic rotor and are placed in a fixed stainless steel tank. When used with a magnetic stirrer, dead zones are minimized. The speed of both the magnetic stirrer and the swing bed can be controlled by a controller.

[0032] 3. The water temperature inside the water jacket can be regulated by a water temperature control system, allowing for rapid heating and cooling; the built-in air frame ensures full contact to guarantee uniform heating; the bag is equipped with a temperature probe, which can provide real-time feedback and control of the temperature via a controller.

[0033] 4. The storage bag can control the temperature through the cooperation of a temperature probe and a controller, and the pH can be controlled through the cooperation of a pH probe and a controller. The controller controls the rotation speed of the rotating bed reactor or magnetic stirrer, which greatly improves the reliability of virus inactivation hydrolysis and significantly reduces costs and labor intensity. Attached Figure Description

[0034] Figure 1 This is a schematic diagram of the overall structure of Embodiment 1 of this application;

[0035] Figure 2 This is a cross-sectional view illustrating the internal structure of Embodiment 1 of this application;

[0036] Figure 3 This is a schematic diagram illustrating the magnetic rotor in Embodiment 2 of this application;

[0037] Figure 4 This is a flowchart illustrating the inactivation method according to an embodiment of this application.

[0038] Explanation of reference numerals in the attached diagram: 1. Storage bag; 11. Inlet; 12. Outlet; 13. Sampling port; 2. External jacket bag; 21. Water inlet; 22. Water outlet; 3. Water jacket; 4. Temperature probe; 5. pH probe; 6. Air inlet valve; 7. Air outlet valve; 71. Pressure gauge; 8. Magnetic rotor; 9. Stainless steel tank; 10. Magnetic stirrer. Detailed Implementation

[0039] The following is in conjunction with the appendix Figure 1-4 This application will be described in further detail.

[0040] This application discloses an inactivation hydrolysis device.

[0041] Example 1

[0042] Reference Figure 1 and Figure 2 An inactivation hydrolysis device includes a hollow and closed storage bag 1 and a heating component for heating the storage bag 1. The storage bag 1 has an inlet 11 and an outlet 12. During the inactivation hydrolysis process, liquid is added into the storage bag 1 through the inlet 11, and the heating component is used to heat and react the liquid.

[0043] The storage bag 1 is made of a transparent, flexible membrane material. Before use, it requires pre-sterilization by gamma ray irradiation. Therefore, it can be used directly without secondary sterilization during subsequent use. During the reaction process, the transparent storage bag 1 allows for convenient real-time observation by staff. After adding the liquid, pressing the flexible storage bag 1 can agitate the liquid. The entire reaction, including inactivation and hydrolysis, can occur inside the storage bag 1, eliminating the need for frequent container changes. The inlet 11 and outlet 11 are also included. 12 are set on opposite sides of the liquid storage bag 1. In this embodiment, the liquid inlet 11 on the liquid storage bag 1 is defined as the upper part, and the liquid outlet 12 on the liquid storage bag 1 is defined as the lower part. A sampling port 13 is provided on the upper part of the liquid storage bag 1. After the liquid inside the liquid storage bag 1 has reacted for a certain period of time, the staff can take out a certain amount of liquid inside the liquid storage bag 1 for testing through the sampling port 13. During the sampling process, the liquid storage bag 1 is filled with compressed air to maintain a positive pressure state, which facilitates sampling. The sampling process is carried out in a sealed environment, resulting in minimal pollution.

[0044] The inlet 11, outlet 12 and sampling port 13 of the liquid storage bag 1 are all connected to sterile quick connectors through pipelines. An air filter membrane is installed in the connected pipeline to ensure that the inside of the system is a sterile environment and to ensure that the liquid inside the liquid storage bag 1 does not leak. The air filter membrane connected in the pipeline can ensure that the entire system is sterile for the experiment.

[0045] Reference Figure 1 and Figure 2 The heating assembly includes an outer jacket bag 2 disposed outside the liquid storage bag 1. The outer jacket bag 2 is fitted over the liquid storage bag 1 and is made of the same material as the liquid storage bag 1, and is also transparent. Pipes connecting the inlet 11, outlet 12, and sampling port 13 of the liquid storage bag 1 pass outward through the outer jacket bag 2, and are sealed at the point of entry. A hollow water jacket 3 is formed between the outer jacket bag 2 and the liquid storage bag 1. An inlet 21 is provided above the outer jacket bag 2, and an outlet 22 is provided below the outer jacket bag 2. Both the inlet 21 and the outlet 22 communicate with the interior of the water jacket 3, and the outlet 22... Both the inlet and outlet 21 are connected to pipelines, and air filter membranes are installed inside the pipelines. During the inactivation and hydrolysis process, a certain amount of water is added into the water jacket 3 through the inlet 21. A water temperature control system is connected to the pipeline between the inlet 21 and the outlet 22. The water temperature control system includes a hot water system and a cooling water system. During the inactivation and hydrolysis process, when it is necessary to increase the temperature of the water in the water jacket 3, the hot water control system circulates and heats the water in the water jacket 3. When it is necessary to decrease the temperature of the water in the water jacket 3, the cooling water system circulates and cools the water in the water jacket 3, thereby achieving rapid heating and cooling.

[0046] Furthermore, an inflatable frame is provided in the water jacket 3 between the outer jacket bag 2 and the liquid storage bag 1. After inflation, the inflatable frame can support the outer jacket bag 2 and the liquid storage bag 1, and ensure that the distance between the outer jacket bag 2 and the liquid storage bag 1 is kept at a fixed distance, so that the water in the water jacket 3 can evenly wrap the liquid storage bag 1, thereby ensuring that the temperature rise or fall can be evenly controlled.

[0047] Reference Figure 1 and Figure 2 A temperature probe 4 and a pH probe 5 are installed inside the storage bag 1. The temperature probe 4 can detect the temperature of the liquid inside the storage bag 1 in real time, and the pH probe 5 can detect the acidity or alkalinity of the liquid inside the storage bag 1 in real time. The inactivation hydrolysis device also includes a controller, which is electrically connected to the temperature probe 4 and the pH probe 5. The controller can also be connected to a water temperature control system. The controller can provide real-time feedback and control the temperature inside the water jacket 3. The water temperature can be adjusted according to actual needs, thereby controlling the temperature of the liquid inside the storage bag 1. The pH probe 5 installed inside the storage bag 1 can monitor the acidity or alkalinity of the liquid inside the storage bag 1 in real time. When the acidity or alkalinity of the liquid exceeds or falls below the design requirements, the pH probe 5 detects the signal and transmits it to the controller. The controller then adjusts the acidity or alkalinity of the liquid by supplying liquid into the storage bag 1 through the inlet 11, or by introducing gas into the storage bag 1 to adjust the pH value of the liquid.

[0048] An air inlet valve 6 and an air outlet valve 7 are connected above the storage bag 1, and a pressure gauge 71 is connected to the air outlet valve 7. When it is necessary to add liquid into the storage bag 1, the operator can first release the pressure inside the storage bag 1 through the air outlet valve 7, so that there is no positive pressure inside the storage bag 1, thus facilitating the filling of liquid into the storage bag 1 through the liquid inlet 11. When the pH value inside the storage bag 1 exceeds the standard or is lower than the normal value, gas can be added into the storage bag 1 through the air inlet valve 6. After the inactivation and hydrolysis are completed, the operator needs to first close the air inlet valve 6, connect the air inlet valve 6 to sterile compressed air, open the air inlet valve 6, and gradually fill the storage bag 1 with gas of a certain pressure, so that the liquid inside the storage bag 1 can be quickly discharged through the liquid outlet 12. During the process of adding gas into the storage bag 1, the pressure inside the storage bag 1 can be monitored in real time through the pressure gauge 71.

[0049] Reference Figure 1 and Figure 2 The inactivation and hydrolysis device also includes a swing bed reactor, which is connected to a controller. When the liquid is added to the storage bag 1 and the capacity of the storage bag 1 is less than 20L, the operator places the storage bag 1 and the outer jacket bag 2 on the swing bed reactor and swings them. The swinging of the swing bed allows the virus extinguishing agent and the virus inside the storage bag 1 to come into full contact and ensures uniform mixing, which greatly improves the reliability of virus inactivation and hydrolysis and reduces labor intensity, avoiding the need for operators to mix and stir. During the swinging process of the swing bed reactor, the controller can control the swing speed to facilitate better and faster uniform mixing of the liquid inside the storage bag 1.

[0050] The implementation principle of the inactivation hydrolysis device in this application embodiment is as follows: when it is necessary to inactivate and hydrolyze the virus, less than 20L of liquid is added into the storage bag 1. The virus inactivating agent and the virus can be fully contacted and mixed through the rotating bed reactor. After the mixing is completed, the liquid in the storage bag 1 is cooled and heated through the water temperature control system until the liquid in the storage bag 1 is inactivated and hydrolyzed.

[0051] Example 2

[0052] Reference Figure 1 and Figure 3The difference between this embodiment and Embodiment 1 is that when the liquid added to the storage bag 1 is more than 20L and less than 100L, a magnetic rotor 8 is installed inside the storage bag 1. The inactivation hydrolysis device includes a stainless steel tank 9 and a magnetic stirrer 10. The stainless steel tank 9 is mounted on the magnetic stirrer 10, and the stainless steel tank 9 has an observation window and holes for interfaces with various devices. The storage bag 1 containing the liquid and the outer jacket bag 2 can be placed inside the stainless steel tank 9. The magnetic stirrer 10 and the magnetic rotor 8 cooperate with each other. The magnetic stirrer 10 drives the magnetic rotor 8 to rotate. The magnetic stirrer 10 is connected to the controller, which can control the magnetic stirrer 10 and the magnetic rotor 8, thereby controlling the stirring speed of the liquid inside the storage bag 1. When the liquid inside the storage bag 1 is greater than 20L but less than 100L, the swing bed reactor can no longer fully mix the liquid. The combination of the magnetic rotor 8, the stainless steel tank 9 and the magnetic stirrer 10 can minimize the problem of dead corners during the stirring process, making the mixing more uniform.

[0053] The implementation principle of Example 2 is as follows: When it is necessary to inactivate and hydrolyze the virus, a liquid of more than 20L and less than 100L can be added into the storage bag 1. The liquid is stirred by the magnetic rotor 8, the stainless steel tank 9 and the magnetic stirrer 10 so that the virus inactivating agent and the virus can come into full contact and mix. After mixing, the liquid in the storage bag 1 is cooled and heated by the water temperature control system until the liquid in the storage bag 1 is inactivated and hydrolyzed.

[0054] This application also discloses a method for deactivating a deactivating hydrolysis device.

[0055] Reference Figure 2 , Figure 3 and Figure 4 An inactivation method for an inactivation hydrolysis device includes the following steps:

[0056] S1: Feeding;

[0057] Open the vent valve 7 to release the pressure inside the liquid storage bag 1, so that there is no positive pressure inside the liquid storage bag 1;

[0058] Aseptically connect the sterile quick connector at the inlet 11 to the liquid supply source. Apply pressure from the liquid supply source to allow the liquid to enter the storage bag 1. During the liquid addition process, ensure that the amount of liquid added to the storage bag 1 does not exceed 80% of the total volume of the storage bag 1.

[0059] After adding the liquid, disconnect the sterile quick connector at the inlet 11 and close the exhaust valve 7.

[0060] S2: Inactivation;

[0061] Open the vent valve 7 to release the pressure inside the liquid storage bag 1, so that there is no positive pressure inside the liquid storage bag 1;

[0062] Aseptically connect the sterile quick connector at the inlet to the liquid supply source, apply pressure to the liquid supply source to allow the virus harvesting liquid to enter the storage bag 1, and control the total amount of liquid added to not exceed 80% of the total volume of the storage bag 1;

[0063] Add PBS solution and perform a top wash through inlet 11. The top wash method can replace a high unit of filtrate.

[0064] The virus inactivating agent β-propiolactone was diluted to a concentration of 1:4000 and then added into the storage bag 1 through the inlet 11.

[0065] Close the sterile quick connector at the inlet 11 and close the exhaust valve 7;

[0066] Based on the volume of the liquid in the storage bag 1, adjust the stirring speed of the swing bed reactor or magnetic stirrer 10, and adjust the water temperature of the water jacket 3 to 2-8℃ through the controller, and continue the reaction for 24 hours.

[0067] S3: Hydrolysis;

[0068] After inactivation is completed, the water temperature in the water jacket 3 is raised to 37°C by the controller, and the storage bag 1 is continuously heated for 23 hours to completely hydrolyze the inactivating agent.

[0069] The pH value of the liquid inside the storage bag 1 is monitored by pH probe 5, and NaOH solution is added into the storage bag 1 through inlet 11 to adjust the pH value of the virus inactivation solution to the specified acidity or alkalinity.

[0070] After hydrolysis, the virus inactivation solution is discharged from outlet 12.

[0071] S4: Discharge;

[0072] After the inactivation and hydrolysis are complete, the inactivation solution needs to be removed and proceeded to the next process. During the discharge process, the following operations are performed:

[0073] Close all valves and interfaces except for the air inlet valve 6, and at the same time close the temperature controller and pH controller, and adjust the oscillation speed of the oscillating bed reactor or the stirring speed of the magnetic stirrer 10 to 0.

[0074] Connect the air inlet valve 6 to a sterile compressed air source and adjust the air intake to maintain the pressure inside the liquid storage bag 1 within a certain range of 0.05-0.1 MPa.

[0075] Connect the sterile quick connector at the outlet 12 end to the container, and then open the outlet 12 to discharge the inactivated solution.

[0076] After all the inactivation solution is drained, the entire storage bag 1 needs to be autoclaved before disposal.

[0077] The above are all preferred embodiments of this application, and are not intended to limit the scope of protection of this application. Therefore, all equivalent changes made in accordance with the structure, shape and principle of this application should be covered within the scope of protection of this application.

Claims

1. An inactivation hydrolysis device, characterized in that: The system includes a hollow and sealed liquid storage bag (1) made of a transparent flexible membrane material. The liquid storage bag (1) has an inlet (11) and an outlet (12) connected to both the inlet (11) and outlet (12). A heating assembly for water bath heating of the liquid storage bag (1) is provided outside the liquid storage bag (1). The heating assembly includes an outer jacket bag (2) fitted over the liquid storage bag (1). The outer jacket bag (2) and the liquid storage bag (1) are made of the same material. A hollow water jacket (3) is formed between the outer jacket bag (2) and the liquid storage bag (1). The sterile quick connector extends outward through the outer jacket bag (2). The outer jacket bag (2) has a water inlet (21) and an outlet (22) connected by a pipeline. A water temperature control system is provided; an air-filled frame is provided in the water jacket (3) between the outer jacket bag (2) and the storage bag (1); a magnetic rotor (8) is provided inside the storage bag (1); the inactivation hydrolysis device includes a stainless steel tank (9), the outer jacket bag (2) and the storage bag (1) are located inside the stainless steel tank (9), a magnetic stirrer (10) that cooperates with the magnetic rotor (8) is provided outside the stainless steel tank (9), and the magnetic stirrer (10) is connected to the controller; a temperature probe (4) and a pH probe (5) are provided inside the storage bag (1), and a controller is provided outside the outer jacket bag (2), and the controller is electrically connected to the temperature probe (4) and the pH probe (5); an air inlet valve (6) and an air outlet valve (7) are connected to the storage bag (1), and a pressure gauge (71) is connected to the air outlet valve (7).

2. The inactivation hydrolysis device according to claim 1, characterized in that: The inactivation hydrolysis device also includes a swing bed reactor, the outer jacket bag (2) and the storage bag (1) can be placed on the swing bed reactor, and the swing bed reactor is connected to the controller.

3. The inactivation hydrolysis device according to claim 1, characterized in that: The liquid storage bag (1) is also provided with a sampling port (13), and a sterile quick connector is connected to the sampling port (13).

4. A method for deactivating the deactivating hydrolysis device as described in any one of claims 1 to 3, characterized in that: Includes the following steps: Feeding: The sterile quick connector on the liquid inlet (11) is connected to the liquid supply source, so that the liquid enters the inside of the storage bag (1); Inactivation: Add virus harvesting solution to the inside of the storage bag (1), add PBS solution to the inside of the storage bag (1) and perform top washing, dilute the virus inactivating agent β-propiolactone to a concentration of 1:4000 and add it to the inside of the storage bag (1), then place the outer jacket bag (2) and the storage bag (1) on the swing bed reactor or stir by a magnetic stirrer (10). During the stirring process, the water temperature of the water jacket (3) is controlled at 2-8℃ by the water temperature control system and inactivation is continued for 24 hours. Hydrolysis: The water temperature inside the water jacket (3) is raised to 37°C by the water temperature control system and heated for 23 hours to completely hydrolyze the inactivating agent. During the hydrolysis process, the value detected by the pH probe (5) is continuously observed. Then, NaOH solution is added to the storage bag (1) to adjust the pH value of the virus inactivating solution to reach the specified acidity or alkalinity. Discharge: Take out the inactivated liquid after the inactivation and hydrolysis are completed for the next process, and dispose of the used outer jacket bag (2) and storage bag (1) after high temperature sterilization.

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