CN115725413A - Integrated cell medicine closed production system - Google Patents

Abstract

The present invention relates to the field of cell drug production, in particular to an integrated closed cell drug production system, comprising a sterile isolator and a multi-chamber carbon dioxide incubator directly connected to the sterile isolator, the sterile isolator includes a control Cabinet, transfer window and operation cabin. After the transfer door on the transfer window is opened, it can be docked with the operation chamber on the operation cabin. The front of the operation chamber is the operation surface, and the back of the operation chamber is docked with the multi-chamber carbon dioxide incubator; In the present invention, the pollution risk caused by the transfer of cell drugs between the incubator and the operating chamber of the aseptic isolator through the transfer interface during the cultivation process is solved, and the incubator is directly connected to the operating chamber of the aseptic isolator Docking, open the door inside the operation chamber, when the operation chamber of the aseptic isolator needs to be operated in a sterile state, you can directly open the door for operation, and it does not need to spend a long time to put the culture container between the culture chamber and the aseptic isolator transfer between.

Description

An integrated closed cell drug production system

technical field

The invention relates to the technical field of cell drug production, in particular to an integrated closed cell drug production system.

Background technique

In the existing preparation process of producing cell drugs in a space-tight manner, in the cell preparation process, the existing scheme adopts the method of sterilizing the blood sample of the cells to be prepared from the outer surface of the transfer window of the sterile isolator, and then passing Into the operating chamber of the aseptic isolator, after the separation, extraction, activation, modification and other operations of the cells are completed in the operating chamber, they are placed in the culture container, and then the medium is added, and then transferred to the external incubator through the transfer interface To cultivate, the incubator in this way is generally separated from the aseptic isolator. Only when the cultured cells need to be operated or the liquid is changed, the incubator is docked with the aseptic isolator, and then the culture container is removed from the culture. Take out the box for operation. This method mainly has the following defects:

1) Every time an operation is required, the incubator needs to be transferred from the cultivation position to the side of the aseptic isolator for docking. The transfer of the culture container requires a lot of work, and each transfer takes a long time.

2) When the incubator is docked with the aseptic isolator, in order to achieve aseptic docking, it is necessary to design various aseptic connection methods, but no matter which method is used, there is a certain risk of contamination.

Contents of the invention

The purpose of the present invention is to solve the shortcomings in the prior art, and propose an integrated closed production system of cell medicine.

In order to achieve the above object, the present invention adopts the following technical solutions:

An integrated closed production system for cell medicines, including a sterile isolator and a multi-chamber carbon dioxide incubator directly connected to the sterile isolator, the sterile isolator includes a control cabinet, a transfer window and an operating cabin, the transfer window After the transfer door on the top is opened, it can be docked with the operation chamber on the operation cabin. The front of the operation chamber is the operation surface, and the back of the operation chamber is docked with the multi-chamber carbon dioxide incubator;

There are a number of installation holes for installing the culture chamber unit on the butt flange of the connection end of the multi-chamber carbon dioxide incubator. The culture chamber unit is placed with a culture container, and each front of the culture chamber unit is equipped with an independent culture chamber door. The chamber door can be opened independently into the operating chamber.

Preferably, the transfer door on the transfer window is equipped with an openable transfer door cover, and a hydrogen peroxide steam sterilizer is arranged in the transfer window.

Preferably, the operating cabin of the aseptic isolator adopts a one-way flow design, and the interior of the operating chamber meets the A-level cleanliness requirements required by GMP.

Preferably, a glass operation door is installed on the operation surface of the operation cavity, and sterile operation gloves extending inward are installed on the glass operation door.

Preferably, a microscope, a centrifuge, a camera, a material rack, a temperature control box and a pipette gun are also installed inside the operating chamber.

Preferably, one side of the bottom of the operation chamber is equipped with a waste liquid outlet and a waste outlet, the waste liquid outlet is connected to an external waste liquid receiving barrel through a conduit, and the waste outlet is connected to an external waste collection bag .

Preferably, the multi-chamber carbon dioxide incubator is docked with the back of the operating chamber of the aseptic isolator through the docking flange, and the butt joint is provided with a gasket for sealing, and the culture chamber unit and the docking flange are also sealed by sealing Gasket seal.

Preferably, the multi-chamber carbon dioxide incubator can be configured with multiple culture chamber units, and the carbon dioxide concentration, temperature and humidity of each culture chamber unit can be independently controlled.

The beneficial effects of the present invention are:

In the present invention, the risk of contamination caused by the frequent transfer of cell medicines between the incubator and the operation cavity of the aseptic isolator through the transfer interface during the cultivation process is solved.

Moreover, the incubator is directly connected to the operating cavity of the aseptic isolator, and the door is opened inside the operating cavity. When the operating cavity of the aseptic isolator needs to be operated in a sterile state, the door can be directly opened for operation without spending a long time. Time to transfer culture containers between culture chambers and sterile isolators.

Description of drawings

Fig. 1 is a structural schematic diagram of an integrated cell drug airtight production system proposed by the present invention;

Fig. 2 is a schematic diagram of the backside structure of the operating cavity proposed by the present invention;

Fig. 3 is a schematic structural view of the multi-chamber carbon dioxide incubator proposed by the present invention.

In the figure: 10, sterile isolator; 40, multi-chamber carbon dioxide incubator; 1, electrical cabinet; 2, transfer window; 3, operation cabin; 201, transfer window cover; 202, transfer door; 301, operation chamber 302, glass operation door; 303, sterile operating gloves; 304, centrifuge; 305, temperature control box; 306, microscope; 307, material rack; 308, waste liquid outlet; 309, waste liquid receiving bucket; 311, socket; 312, camera; 313, pipette gun; 401, docking flange; 402, culture chamber door; 403, culture chamber unit; 404, culture container.

Detailed ways

The following will clearly and completely describe the technical solutions in the embodiments of the present invention with reference to the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only some, not all, embodiments of the present invention.

Referring to Figures 1-3, an integrated closed production system for cell medicines includes an aseptic isolator 10 and a multi-chamber carbon dioxide incubator 40 directly connected to the aseptic isolator 10, and the aseptic isolator 10 includes a control cabinet 1 , the transmission window 2 and the operation cabin 3, the transmission door 202 on the transmission window 2 can be docked with the operation chamber 301 on the operation cabin 3 after being opened, the front of the operation chamber 301 is the operation surface, and the back of the operation chamber 301 is connected to the multi- Cavity carbon dioxide incubator 40 docking;

The butt flange 401 at the connection end of the multi-chamber carbon dioxide incubator 40 is provided with several installation holes for installing the culture chamber unit 403, the culture chamber unit 403 is provided with a culture container 404, and each front of the culture chamber unit 403 is provided with an independent The culture chamber door 402 can be independently opened into the operation chamber 301 .

Wherein, the transfer door 202 on the transfer window 2 is equipped with an openable transfer door cover 201, and the transfer window 2 is equipped with a hydrogen peroxide steam sterilizer, so that the transfer window 2 has a rapid hydrogen peroxide steam sterilization function , can achieve rapid surface sterilization of materials.

Moreover, the operation cabin 3 of the aseptic isolator 10 adopts a one-way flow design, and the interior of the operation cavity 301 meets the A-level cleanliness requirements required by GMP, and the operation surface of the operation cavity 301 is equipped with a glass operation door 302, and the glass operation door 302 A sterile operating glove 303 extending inward is installed on the top, and a microscope 306, a centrifuge 304, a camera 312, a material rack 307, a temperature control box 305, a pipetting gun 313, and a power supply socket 311 are also installed inside the operating cavity 301. , There is also a hydrogen peroxide steam sterilizer.

At the same time, the bottom side of the operation chamber 301 is equipped with a waste liquid outlet 308, and the waste liquid outlet 308 is connected to the external waste liquid receiving barrel 309 through a conduit; the bottom side of the operation chamber 301 is equipped with a waste outlet 310, The waste delivery port 310 is connected with an external waste collection bag.

Among them, the multi-chamber carbon dioxide incubator 40 is docked with the back of the operation cavity 301 of the aseptic isolator 10 through the docking flange 401, and the joint is provided with a gasket for sealing, and there is a gap between the culture chamber unit 403 and the docking flange 401. It is also sealed by a gasket.

Moreover, the multi-chamber carbon dioxide incubator 40 can be configured with a plurality of culture chamber units 403, and the carbon dioxide concentration, temperature, and humidity of each culture chamber unit 403 can be independently controlled, and the culture chamber units 403 of the multi-chamber carbon dioxide incubator 40 The volume of the cell can be designed according to the volume of cells that need to be cultured in a batch to meet the culture needs of a batch of products.

In this embodiment, before cell preparation, various consumables and instruments required for preparation that can withstand long-term hydrogen peroxide steam sterilization are placed in the operating chamber 301 of the aseptic isolator, and the centrifuge 304 and the intended use The door of the culture chamber unit 403 for cell culture prepared this time is opened, the operation glass door 302 of the operation chamber 301 is closed, hydrogen peroxide steam sterilization is started, and the interior of the operation chamber 301 and the culture chamber unit 403, centrifuge The 304 centrifuge chamber is fully hydrogen peroxide vapor sterilized.

After the operation cavity 301 is sterilized, open the transfer window cover 201, put the raw materials and consumables that cannot withstand long-term sterilization into the transfer window 2, close the transfer window cover 201, and put the transfer window 2 and the transfer window 2 The outer surfaces of the raw materials and consumables inside are quickly sterilized by hydrogen peroxide steam. After the sterilization, the transfer door 203 is opened to transfer the raw materials and consumables into the operation chamber 301, and then the cells can be processed according to the cell preparation process. Preparation operation: After the cell preparation is completed, put the cells to be cultured into the culture container 404, then put the culture container 404 into the culture chamber unit 403 with the door open, and close the culture chamber door 402 to start cell culture.

During the cell culture process, when observation is required, the operation chamber 301 is first sterilized by hydrogen peroxide steam. After the sterilization is completed, the culture chamber door 402 of the culture chamber unit 403 where the cells to be observed are located is opened, and the cell culture container 404 is taken out, and the cell culture container 404 that can be directly observed can also be directly placed on the microscope 306 to observe and take pictures; if a sample is required to be observed, then the cell culture container 404 is opened, and a part is drawn out with a pipette gun 313 for observation . After the observation is over, the culture container 404 is sealed and put back into the culture chamber unit 403, the culture chamber door 402 is closed, the culture is continued, and one observation is over.

During the cell culture process, when the liquid needs to be changed, the operation chamber 301 is first sterilized by hydrogen peroxide steam. After the sterilization is completed, the culture chamber door 402 of the culture chamber unit 403 where the cells needing to be changed is opened, and the cells Take out the culture container 404 and open it, pipette the liquid into the centrifuge bottle with the pipette gun 313, then put the centrifuge bottle into the centrifuge 304 for centrifugation, after centrifugation, suck out the unnecessary liquid and put it into the designated container, and continue to cultivate The concentrated cells are added back to the culture container 404, and then new medium is added, put back into the culture chamber unit 403, and the culture is continued.

Among them, in the operating chamber 301 of the aseptic isolator, a temperature control box 305 can be installed to store cells or reagents that need to be kept at low or high temperatures, so as to avoid damage to the quality of reagents or cells caused by long-term exposure to normal temperature in the operating chamber. Influence.

Wherein, the operation cavity 301 of the aseptic isolator can be equipped with a solid waste delivery port 310 , and during the cell preparation operation, if a lot of solid waste is generated, it can be sent out through the solid waste delivery port 310 .

Wherein, on the operating cavity 301 of the aseptic isolator, a waste liquid outlet 308 can be installed. During the cell preparation operation, if more liquid waste is generated, it can be sent out to the waste liquid bucket 309 through the waste liquid outlet 308 , and then removed for processing.

Wherein, in the operation cavity 301 of the aseptic isolator, a camera 312 can be installed to record all the operations in the operation cavity 301 of the aseptic isolator during the whole cell production process, which is convenient for management personnel to watch in real time, and also convenient for monitoring The entire production operation process is traceable.

Among them, the multi-chamber carbon dioxide incubator 40 can be configured with multiple culture chamber units 403, and the carbon dioxide concentration, temperature, and humidity of each culture chamber unit 403 can be independently controlled without interfering with each other; and each of the multi-chamber carbon dioxide incubator 40 Each culture chamber unit 403 can optionally control the oxygen concentration to meet the requirements of the culture environment with special oxygen concentration.

In the present invention, the pollution risk caused by the transfer of cell drugs between the incubator and the operating chamber of the aseptic isolator through the transfer interface during the cultivation process is solved; and the incubator is directly connected to the operating chamber of the aseptic isolator Docking, open the door inside the operation chamber, when the operation chamber of the aseptic isolator needs to be operated in a sterile state, you can directly open the door for operation, and it does not need to spend a long time to put the culture container between the culture chamber and the aseptic isolator transfer between.

At the same time, the incubator system adopts a customized design, which can be configured with a suitable size of culture chamber unit according to the actual cultivation needs of cell drugs, so as to maximize the use of the volume in the culture chamber; the incubator system can be configured with multiple independent culture chambers according to needs Each culture chamber unit adopts a completely independent airtight design, which can independently control the culture environment in the culture chamber to meet the needs of simultaneous cultivation of multiple batches of products.

The above is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto, any person familiar with the technical field within the technical scope disclosed in the present invention, according to the technical solution of the present invention Any equivalent replacement or change of the inventive concepts thereof shall fall within the protection scope of the present invention.

Claims (9)

1. an integrated cell medicine closed production system, comprising an aseptic isolator (10) and a multi-chamber carbon dioxide incubator (40) directly docked with the aseptic isolator (10), it is characterized in that the aseptic isolator (10) The bacteria isolator (10) includes a control cabinet (1), a transfer window (2) and an operation cabin (3). After the transfer door (202) on the transfer window (2) is opened, it can be connected with the operation chamber on the operation cabin (3). body (301) docking, the front of the operating cavity (301) is the operating surface, and the back of the operating cavity (301) is docked with the multi-chamber carbon dioxide incubator (40); The butt flange (401) at the connecting end of the multi-chamber carbon dioxide incubator (40) is provided with several installation holes for installing the culture chamber unit (403), and a culture container (404) is placed in the culture chamber unit (403). Each front of the culture chamber unit (403) is provided with an independent culture chamber door (402), and the culture chamber door (402) can be independently opened into the operation chamber (301). 2. The integrated closed production system of cell medicine according to claim 1, characterized in that, the transfer door (202) on the transfer window (2) is equipped with an openable and closable transfer door cover (201) , and a hydrogen peroxide steam sterilizer is arranged in the transfer window (2). 3. The integrated closed production system of cell medicine according to claim 1, characterized in that, the operating cabin (3) of the aseptic isolator (10) adopts a one-way flow design, and the operating cavity (301 ) The interior meets the requirements of Class A cleanliness required by GMP. 4. The integrated closed production system of cell medicine according to claim 3, characterized in that, the operating surface of the operating cavity (301) is equipped with a glass operating door (302), and the glass operating door (302) is Inwardly extending sterile operating gloves (303) are installed. 5. An integrated closed production system for cell medicine according to claim 1, characterized in that, a microscope (306), a centrifuge (304), a camera (312 ), material rack (307), temperature control box (305) and pipette gun (313). 6. An integrated closed production system for cell medicine according to claim 1, characterized in that a waste liquid outlet (308) is arranged on the bottom side of the operation chamber (301), and the waste liquid outlet (308) 308) is connected with the external waste liquid receiving barrel (309) through a conduit. 7. An integrated closed cell drug production system according to claim 1, characterized in that a waste delivery port (310) is arranged on the bottom side of the operation chamber (301), and the waste delivery port ( 310) is connected with the waste collection bag of the outside. 8. A kind of integrated closed production system of cell medicine according to claim 1, characterized in that, the multi-chamber carbon dioxide incubator (40) is connected to the aseptic isolator (10) through the docking flange (401) The back of the operation cavity (301) is butted, and the butt joint is provided with a gasket for sealing, and the culture chamber unit (403) and the docking flange (401) are also sealed by the gasket. 9. The integrated closed production system of cell medicine according to claim 1, characterized in that, the multi-chamber carbon dioxide incubator (40) can be configured with multiple culture chamber units (403), and each culture The carbon dioxide concentration, temperature and humidity of the chamber unit (403) can be independently controlled.

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