CN216141553U - Immune cell production line - Google Patents

Abstract

The application provides an immune cell production line, which comprises a production preparation area, a first clean channel and a clean production area, wherein the first clean channel is arranged in a buffer area between the production preparation area and the clean production area; the cleanliness class of the first clean tunnel is not lower than the clean production area; compare in current immune cell production line, the immune cell production line of this application has that overall layout is compact reasonable, the biological safety is high, investment and the lower advantage of running cost.

Description

Immune cell production line

Technical Field

The application relates to the technical field of biological pharmacy, in particular to an immune cell production line.

Background

With the rapid development of medical technology, the clinical application of cell therapy is becoming more and more extensive, and the way of producing cells by means of small-scale laboratories has not been able to meet the market demand, so the production line for large-scale production of immune cells has come up. The production line for the large-scale production of immune cells needs to meet two requirements: on one hand, each process step of separation, purification, transfection, amplification and the like needs to be carried out under the B-grade clean condition; on the other hand, cross contamination between different batches of products is avoided.

In order to meet the requirements of the two aspects, the existing immune cell production lines mainly have two types, one type is as follows: the immune cell production line comprises a plurality of working areas which are completely and physically isolated from each other, each working area is provided with a separate dressing area, a withdrawing and changing area and a facility for maintaining the environmental conditions of the working areas, the immune cell production line needs to separately control the production environment of each working area, and the immune cell production line has the defect of high investment and operation cost. The other is as follows: the immune cell production line comprises at least one production clean room, wherein a plurality of working areas are distributed in the production clean room, the working areas share a set of facilities for maintaining environmental conditions, and controlled personnel in the production clean room can freely enter and exit any one of the working areas, so that cross contamination risks exist among different working areas.

Therefore, there is a need to develop an immune cell production line, which can not only reduce the investment and operation cost of the production line, but also effectively avoid the problem of cross contamination in the production process.

Disclosure of Invention

Aiming at the defects of the existing immune cell production line, the application provides the immune cell production line, which can not only reduce the investment and the operation cost of the production line, but also effectively improve the problem of cross contamination in the production process.

The application provides an immune cell production line, which comprises a production preparation area, a first clean channel and a clean production area, wherein the first clean channel is a buffer area between the production preparation area and the clean production area, the production preparation area comprises a personnel production preparation area and a material production preparation area which are isolated from each other, the clean production area comprises a plurality of operating rooms which are isolated from each other, and each operating room is respectively provided with an independent environment control system; the first clean tunnel has a cleanliness level not lower than the clean production area.

In some embodiments of the present application, the production preparation area further comprises a second clean channel, the personnel production preparation area and the second clean channel are provided with an openable and closable through opening therebetween, and the material production preparation area and the second clean channel are provided with an openable and closable through opening therebetween.

In some embodiments of the present application, the staff production preparation area comprises a first changing area and a second changing area, the first changing area having a cleanliness level not lower than the clean production area; openable and closable through holes are respectively formed between the first changing area and the first clean channel and between the first changing area and the second clean channel; an openable and closable through opening is arranged between the second clothes changing area and the second clean channel.

In some embodiments of the present application, the personnel production preparation area further comprises a refuge area, and an openable and closable through opening is provided between the refuge area and the first clean channel.

In some embodiments of the present application, the material production preparation area includes a blood sample pretreatment area and a production material preparation area, and the blood sample pretreatment area and the production material preparation area are disposed adjacent to each other.

In some embodiments of the present application, the material production preparation area includes a hazardous waste chamber disposed adjacent to the production feedstock preparation area.

In some embodiments of the present application, the danger is useless the room and is equipped with at least one air exit, the air exit is connected with the exhaust fan, the exhaust fan set up in the outside of immune cell production line.

In some embodiments of the present application, the material production preparation area and/or the clean production area is provided with production equipment requiring gas supply; the material production preparation area comprises a gas supply chamber, and the gas supply chamber is connected with the production equipment needing gas supply through a gas transmission pipeline.

In some embodiments of the present application, each of the operation chambers is provided with an incubator to be supplied with gas; the gas transmission pipeline comprises a main gas transmission pipeline and branch gas transmission pipelines which are branched at the operating rooms of the main gas transmission pipeline, and the branch gas transmission pipelines are communicated with the incubator needing gas supply.

In some embodiments of the present application, the production preparation area, the first clean channel, and the clean production area are respectively provided with a plurality of clean air inlets and a plurality of air return inlets, and the clean air inlets and the air return inlets are connected with air conditioners; and at least one clean air inlet and at least one return air inlet are respectively arranged in each operating room.

The application provides an immune cell production line, the immune cell production line is regional with the production preparation and is kept apart through first clean passageway in clean production region, and each control chamber in clean production region keeps apart and independent operation each other, effectively avoids cross contamination's problem, thereby improves the biological safety of immune cell production line. In addition, since each operation room is isolated from each other and operates independently, when only one operation room is operated, only operation services (such as air supply, environmental monitoring, clean air circulation and the like) need to be provided for the operation room, and operation services do not need to be provided for other operation rooms, thereby being beneficial to reducing the operation cost of the immune cell production line. The whole immune cell production line is compact and reasonable in layout, and is favorable for saving land area and further reducing project infrastructure construction cost.

Drawings

The technical solution and other advantages of the present application will become apparent from the detailed description of the embodiments of the present application with reference to the accompanying drawings.

Fig. 1 is a first schematic plan view of an immune cell production line provided in an embodiment of the present application.

Fig. 2 is a schematic plan layout view of an immune cell production line provided in the embodiment of the present application.

Fig. 3 is a schematic plan layout view of the operation chamber in fig. 2.

Fig. 4 is a schematic view showing the connection of the air supply chamber and each operation chamber in fig. 2.

Fig. 5 is a schematic structural view of the gas transmission pipeline in fig. 4.

FIG. 6 is a schematic plan view of the clean air intake ports of the respective regions of the cellular immunization production line shown in FIG. 2.

FIG. 7 is a schematic plan view showing the air return ports of the respective regions of the cellular immune line shown in FIG. 2, and the exhaust ports of the depletion chamber and the air supply chamber.

Detailed Description

The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. It is to be understood that the embodiments described are only a few embodiments of the present application and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present application.

The terms "first", "second" and "first" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Thus, features defined as "first", "second", may explicitly or implicitly include one or more of the described features.

The term "plurality" means two or more unless specifically limited otherwise.

The terms "connected" and "connected" are to be construed broadly, and may, for example, be fixedly connected, detachably connected, or integrally connected. The specific meaning of the above terms in the present application can be understood by those of ordinary skill in the art as appropriate.

The term "immune cell" refers to cells involved in or associated with an immune response, which includes lymphocytes, dendritic cells, monocytes/macrophages, granulocytes, mast cells, and other cells capable of recognizing antigens and producing a specific immune response.

The term "buffer zone" refers to a zone provided at the entrance and exit of a room where a pressure difference needs to be strictly controlled, which is used to separate two zones of different cleanliness in order to prevent the problem of cross-contamination between different environments. In the embodiments of the present application, "buffer" and "buffer area" may be used interchangeably.

The term "cleanliness class" refers to the air cleanliness class in the pharmaceutical product quality management code (revised 2010),

in the embodiments of the present application, unless otherwise expressly stated or limited, "above" or "below" a first feature may include the first and second features being in contact, or may include the first and second features not being in contact but being in contact with another feature therebetween. The embodiment of the present application provides an immune cell production line, as shown in fig. 1 and 2, the immune cell production line 100 includes a production preparation area 1, a first clean tunnel 2 and a clean production area 3, wherein the first clean tunnel 2 is a buffer area between the production preparation area 1 and the clean production area 3, and the first clean tunnel 2 is disposed between the production preparation area 1 and the clean production area 3. The cleanliness class of the first clean tunnel 2 and the clean production area 3 are both class B. Two ends of the first clean channel 2 are respectively provided with an outlet 21 directly leading to the outside of the immune cell production line, and the outlet 21 is a fire-fighting safety outlet.

The production preparation area 1 comprises a personnel production preparation area 11 and a material production preparation area 12 which are isolated from each other, the clean production area 3 comprises a plurality of operation rooms 31 which are isolated from each other, and each operation room 31 is respectively provided with an independent environment control system. The environmental control system may include, for example, a controlled air intake, a controlled air return/exhaust, and a temperature and humidity sensor.

In an embodiment of the present application, the production preparation area 1 further includes a second clean channel 13, an openable and closable through opening is provided between the personnel production preparation area 11 and the second clean channel 13, and an openable and closable through opening is provided between the material production preparation area 11 and the second clean channel 13. The second clean tunnel 13 has a clean level of class C.

In one embodiment of the present application, the personnel production preparation area 11 includes a first changing area 111 and a second changing area 112, and the first changing area 111 has a cleanliness class of class B. Openable and closable through openings are respectively arranged between the first changing area 111 and the first clean channel 2, and between the first changing area 111 and the second clean channel 13, and openable and closable through openings are arranged between the second changing area 112 and the second clean channel 13, that is: all the personnel in the production preparation area 1 enter the first clean tunnel 2 through the first changing area 111 and then enter the clean production area 3. An openable and closable opening is formed between the second changing area 112 and the second clean channel 13. It should be noted that only one-way communication of people is performed between the first changing area 111 and the first clean tunnel 2, and between the first changing area 111 and the second clean tunnel 13; the second changing area 112 and the second clean tunnel 13 are communicated with each other only in one direction. It should be noted that the layout of the first changing area 111 and the second changing area 112 is not particularly limited, and may be selected by the user.

In one embodiment of the present application, the personnel production preparation area 11 further comprises a first ingress and egress buffer 113, the first ingress and egress buffer 113 being a Control Not Classified (CNC) area. The first buffer area 113 is disposed adjacent to the second changing area 112, an openable and closable port is disposed between the first buffer area 113 and the second changing area 112, and the first buffer area 113 and the second changing area 112 are in one-way person communication. Personnel outside the immune cell production line 100 enter the immune cell production line 100 through the first buffer area 113 and then enter the second changing area 112 for changing clothes, disinfecting and the like.

The first input/output buffer 113 is provided with a personnel inlet and a personnel outlet of the whole cell production line, and the personnel inlet and the personnel outlet can be combined into an openable and closable port 114, which is correspondingly in bidirectional communication with the outside of the immune cell production line 100. The personnel entrance and the personnel exit may also be provided independently of each other, i.e.: personnel entry and personnel the export is a openable through-hole respectively, personnel entry with between the outside, and personnel export with all carry out personnel's one-way circulation between the outside.

In one embodiment of the present application, the second changing area 112 includes: a changing buffer region 1121, a men changing region 1122 and a women changing region 1123, wherein the cleaning level of the changing buffer region 1121 is grade D. Openable and closable through holes are respectively formed between the changing buffer region 1121 and the first inlet and outlet buffer region 113, between the changing buffer region 1121 and the men's changing region 1122, and between the changing buffer region 1121 and the women's changing region 1123. The dressing buffer 1121 and the first ingress and egress buffer 113 can perform one-way circulation of people; the clothes changing buffer region 1121 and the man clothes changing region 1122, and the clothes changing buffer region 1121 and the woman clothes changing region 1123 can be communicated in one direction or two directions.

The layout of the men's changing area 1122 and the women's changing area 1123 is the same, and the men's changing area 1122 will be described as an example. The men's changing area 1122 is provided with a class 1 changing room 101 and a class 2 changing room 102, wherein the class 1 changing room 101 is class D and the class 2 changing room 102 is class C. The person performs a shoe changing operation in the changing room No. 1 101, and the person performs a clothes changing, a cap wearing, and a whole body sterilizing operation in the changing room No. 2 102. Openable and closable openings are respectively formed between the No. 1 changing room 101 and the changing buffer region 1121, between the No. 1 changing room 101 and the No. 2 changing room 102, and between the No. 2 changing room 102 and the second clean passage 13. One-way or two-way communication of people can be performed between the changing room 1 101 and the changing buffer region 1121, and between the changing room 2 102 and the second clean passage 13, and only one-way communication of people can be performed between the changing room 1 101 and the changing room 2 102.

In one embodiment of the present application, the personnel production preparation area 11 further comprises a first refurbishment area 115 and a second refurbishment area 116, and the cleanliness levels of the first refurbishment area 115 and the second refurbishment area 116 are both class C. Openable and closable ports are provided between the first retreat region 115 and the second clean path 13, and between the first retreat region 115 and the first buffer area 113. Only one-way communication of people is performed between the first refund area 115 and the second clean tunnel 13, and between the first refund area 115 and the first ingress and egress buffer 113, that is: personnel in the first refund zone 115 cannot directly enter the second clean tunnel 13 and personnel in the first ingress buffer 113 cannot directly enter the first refund zone 115.

Openable and closable ports are provided between the second retreat region 116 and the first clean path 2, and between the second retreat region 116 and the first buffer area 113. The second retreat region 116 and the first clean tunnel 2, and the second retreat region 116 and the first entrance buffer 113 can only have one-way communication of people, that is: personnel in the second refund zone 116 cannot enter directly into the first clean tunnel 2 and personnel in the first ingress buffer 113 cannot enter directly into the second refund zone 116.

In one embodiment of the present application, the material preparation area 12 includes a second input buffer area 121, a blood sample pre-processing area 122 and a production material preparation area 123, wherein the second input buffer area 121 and the blood sample pre-processing area 122 are CNC areas, and the cleaning level of the production material preparation area 123 is class C. The second buffer area 121 is disposed adjacent to the blood sample pretreatment area 122, and the blood sample pretreatment area 122 is disposed adjacent to the raw material preparation area 123. The blood sample pretreatment area 122 and the raw material preparation area 123 do not directly communicate with each other, and only one-way or two-way communication of the blood sample is performed.

The second buffer area 121 is provided with an openable port for one-way or two-way communication of a blood sample with the outside of the immunocyte production line 100. An openable and closable port is provided between the second input/output buffer region 121 and the blood sample pretreatment region 122, so that the blood sample can flow between the second input/output buffer region 121 and the blood sample pretreatment region 122 in one or two directions.

The blood sample pretreatment area 122 is used for receiving, recording and transmitting blood samples, and facilities such as a console, a blood sample placing rack, a computer, a printer and the like can be arranged in the blood sample pretreatment area. Transferring the blood sample that is qualified and approved for the examination to the blood sample pre-treatment area 122, removing the outer package of the blood sample by the personnel in the blood sample pre-treatment area 122 to examine the blood sample again, and placing the blood sample in a secondary container; then, inputting the relevant information of the blood sample meeting the requirements into a computer; finally, the blood sample and associated documents are transferred through the transfer window to the manufacturing materials preparation area 123.

The manufacturing material preparation area 123 is used for further processing of blood samples and preparation of materials required for immune cell production, such as: media, and the like. Facilities such as an operation table, a sterilization apparatus, and a medicine rack may be disposed in the raw material preparation area 123. The production material preparation area 123 and the first clean channel 2 can be communicated in one direction or two directions through a transfer window.

In one embodiment of the present application, the material production preparation area 12 further comprises a hazardous waste chamber 124, and the hazardous waste chamber 124 is disposed adjacent to the production feedstock preparation area 123. The hazardous waste material in the raw material preparation area 123 is transferred to the hazardous waste chamber 124 through a transfer window, and no person is in direct communication between the hazardous waste chamber 124 and other areas. The hazardous waste chamber 124 is a CNC area with an openable and closable opening so that hazardous waste therein can be directly transported to the outside of the immune cell production line 100.

In an embodiment of the present application, the material production preparation area 12 and/or the clean production area 3 is provided with production equipment requiring gas supply, then the material production preparation area 12 further includes a gas supply chamber 125, the gas supply chamber 125 is disposed adjacent to the production raw material preparation area 123, the gas supply chamber 125 is connected to the production equipment requiring gas supply through a gas transmission pipeline, and a gas cylinder is stored in the gas supply chamber 125. The gas supply chamber 125 is a CNC area provided with an openable and closable port to make two-way communication of personnel and gas cylinders with the outside of the immune cell production line 100. Because the gas supply chamber 125 is arranged outside the clean production area 3, the use condition of gas can be conveniently monitored in a centralized manner, and in addition, when the gas cylinder needs to be replaced, external personnel directly enter the gas supply chamber 125 to replace the gas cylinder, so that the pollution caused by the external personnel to the clean production area 3 is effectively avoided.

In one embodiment of the present application, the clean production area 3 is provided with four operation rooms 31 arranged side by side, and the adjacent operation rooms 31 are separated by walls. As shown in fig. 3, each of the operation chambers 31 includes: an operation table 311, a biosafety cabinet 312, a centrifuge 313 and a carbon dioxide incubator 314, wherein the operation table 311 and the biosafety cabinet 312 are arranged side by side on one wall of the operation room 31, and the centrifuge 313 and the carbon dioxide incubator 314 are arranged side by side on the other wall of the operation room 31.

An openable and closable through opening is arranged between each operation chamber 31 and the first clean channel 2, so that the two-way circulation of personnel is realized. Each of the operating chambers 31 is provided with a material transfer window 315 and a waste transfer window 316, and only one batch of production material or one batch of finished products produced through the material transfer window 315 can be transferred at a time, and waste generated in the production process can be transferred only through the waste transfer window 316. The finished products may be sequentially transferred into the blood sample pre-processing region 122 through the material transfer window 315, the transfer window between the production material preparation region 123 and the first clean channel 2, and the transfer window between the blood sample pre-processing region 122 and the production material preparation region 123 for a packaging process, and then transported to the outside of the immune cell production line 100 through the second buffer region 121.

The gas required for the carbon dioxide incubator 314 is provided by the gas supply chamber 125 disposed outside the clean production area 3. As shown in fig. 4 and 5, the gas supply chamber 125 communicates with a carbon dioxide incubator (not shown) in each of the operation chambers 31 through a gas transmission line 103. The gas transmission pipe 103 includes a main gas transmission pipe 1031, and a branch gas transmission pipe 1032 which branches off from the main gas transmission pipe 1031 at each of the operation chambers 31, so as to independently control the gas supply to the carbon dioxide incubators in each of the operation chambers 31.

It should be noted that the facilities and layout of the operation room 31 are not limited specifically, and only need to meet the requirements of current Good manufacturing Practices (cGMP) for cleaning and disinfection, and can be selected according to actual needs.

The arrangement of the clean air inlets of each region of the cellular immune production line is shown in fig. 6, each region is respectively provided with a plurality of clean air inlets 104, each operation chamber 31 is respectively provided with at least one clean air inlet 104, and the clean air inlets 104 are preferably arranged at the ceiling of each region. The clean air of each region is provided by the air conditioning unit 105, the air conditioning unit 105 may be disposed outside the immune cell production line 100 or inside the immune cell production line 100, and in the embodiment of the present application, the air conditioning unit 105 is preferably disposed outside the immune cell production line 100. The air conditioning unit 105 is connected to each of the clean air inlets 104 through an air inlet duct 106, and each of the clean air inlets 104 is independently controlled.

The air return vent layout of the cellular immune production line 100 is shown in fig. 7, at least one air return vent 107 is respectively disposed in each operation chamber 31, and preferably, a height difference is provided between the air return vent 107 and the clean air inlet, for example: the air return opening 107 may be provided at a position near the ground on the wall. The return air inlet 107 is communicated with the air conditioning unit 105 through a return air duct 108.

Fig. 7 also shows the exhaust outlet 109 of the critical waste chamber 124 and the air supply chamber 125, the exhaust outlet 109 is connected with the exhaust fan 110 through the exhaust duct 111, and the exhaust fan 110 is preferably arranged outside the immune cell production line 100. The exhaust fan 110 can directly draw air from the waste air chamber 124 and the air supply chamber 125 to the outside of the immune cell production line 100 and remove contaminants. In addition, the exhaust fan 110 may be connected with a purifying device for purifying the air from the hazardous waste chamber 124 and the air supply chamber 125 to reach the emission standard and then recycling or exhausting the air into the atmosphere. It should be noted that only two air return ports 107 are labeled in fig. 7 as an illustration, and it is understood that, besides the labeled air outlet port 109, other air return ports not labeled in fig. 7 are all the air return ports 107.

In the foregoing embodiments, the descriptions of the respective embodiments have respective emphasis, and for parts that are not described in detail in a certain embodiment, reference may be made to related descriptions of other embodiments.

An immune cell production line provided in the embodiments of the present application is described in detail above. The principle and the implementation of the present application are explained by applying specific examples, and the above description of the embodiments is only used to help understanding the technical solution and the core idea of the present application; those of ordinary skill in the art will understand that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; such modifications or substitutions do not depart from the spirit and scope of the present disclosure as defined by the appended claims.

Claims (6)

1. An immune cell production line, which is characterized by comprising a production preparation area, a first clean passage and a clean production area, wherein the first clean passage is a buffer area between the production preparation area and the clean production area, the production preparation area comprises a personnel production preparation area and a material production preparation area which are isolated from each other, the clean production area comprises a plurality of operation rooms which are isolated from each other, and each operation room is respectively provided with an independent environment control system; the cleanliness class of the first clean tunnel is not lower than the clean production area;

the material production preparation area comprises a blood sample pretreatment area, a production raw material preparation area and a hazardous waste chamber, wherein the blood sample pretreatment area and the production raw material preparation area are adjacently arranged, and the hazardous waste chamber and the production raw material preparation area are adjacently arranged; an operation table and a blood sample placing frame are arranged in the blood sample pretreatment area, an operation table, a sterilization device and a medicine frame are arranged in the production raw material preparation area, the blood sample pretreatment area and the production raw material preparation area transmit materials through a transmission window, the production raw material preparation area and the first clean channel transmit materials through the transmission window, and hazardous waste materials in the production raw material preparation area are transmitted to the hazardous waste chamber through the transmission window; the dangerous waste chamber is provided with at least one air outlet which is connected with an exhaust fan, and the exhaust fan is arranged outside the immune cell production line;

the production preparation area, the first clean channel and the clean production area are respectively provided with a plurality of clean air inlets and a plurality of air return inlets, and the clean air inlets and the air return inlets are connected with air conditioners; each operating room is respectively provided with at least one clean air inlet and at least one return air inlet; the air conditioner is arranged outside the immune cell production line.

2. The immune cell production line of claim 1, wherein the production preparation area further comprises a second clean channel, an openable and closable port is provided between the personnel production preparation area and the second clean channel, and an openable and closable port is provided between the material production preparation area and the second clean channel.

3. The immune cell production line of claim 2, wherein the production preparation area comprises a first dressing area and a second dressing area, the first dressing area having a cleanliness level not lower than the clean production area; openable and closable through holes are respectively formed between the first changing area and the first clean channel and between the first changing area and the second clean channel; an openable and closable through opening is arranged between the second clothes changing area and the second clean channel.

4. The immune cell production line of claim 3, wherein the production preparation area further comprises a retreat region, and an openable and closable port is provided between the retreat region and the first clean channel.

5. The immune cell production line of claim 1, wherein production equipment requiring gas supply is arranged in the material production preparation area and/or the clean production area; the material production preparation area comprises a gas supply chamber, and the gas supply chamber is connected with the production equipment needing gas supply through a gas transmission pipeline.

6. The immune cell production line of claim 5, wherein each of the operating chambers is provided with an incubator to be supplied with air; the gas transmission pipeline comprises a main gas transmission pipeline and branch gas transmission pipelines which are branched at the operating rooms of the main gas transmission pipeline, and the branch gas transmission pipelines are communicated with the incubator needing gas supply.

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