Enzyme-free sterile clean room
By designing an enzyme-free sterile clean room in mRNA vaccine production, and using transparent barriers and purification air conditioning systems to control pressure differences, the problem of human enzyme contamination is solved, and the stability of an enzyme-free sterile environment and the efficiency of drug production is achieved.
Patent Information
- Application Number
- CN202421535763.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Utility models(China)
- Current Assignee / Owner
- Filing Date
- 2024-07-01
- Publication Date
- 2025-07-18
- Estimated Expiration
- 2034-07-01
AI Technical Summary
Prior Art During the mRNA vaccine production process, human enzymes enter the production environment, resulting in the failure of drug research and development or production, affecting the production speed of operators.
Design an enzyme-free sterile clean room, including an enzyme-free sterile clean area, a one-way inlet and exit of the abortion area and a logistics area, use an operable transparent barrier system to isolate the abortion area and an enzyme-free sterile clean area, and set up a purification air conditioning system in each area to control the indoor pressure difference to maintain an enzyme-free sterile environment.
Effectively maintain an enzyme-free and sterile environment, avoid operators wearing protective clothing with head covers and affecting the speed of drug production, and ensure the stability and efficiency of drug production.
Smart Images
Figure CN223119638U_ABST
Abstract
Description
Technical Field
[0001] The utility model belongs to the technical field of clean rooms, and particularly relates to a clean room without enzymes and bacteria. Background Art
[0002] The outbreak of the COVID-19 pandemic has brought messenger ribonucleic acid (mRNA) vaccines into the public eye, sparking interest and anticipation in the field of RNA therapy.
[0003] An mRNA vaccine is a nucleic acid preparation that prepares mRNA through processes such as synthesis and transcription, introduces an exogenous target gene sequence into body cells with a specific delivery system, expresses the target protein, and stimulates a specific immunological reaction in the body, thereby enabling the body to obtain immune protection.
[0004] The R & D process of mRNA vaccines includes: antigen selection, gene sequencing, selection and optimization of the gene sequence encoding the target antigen, screening of modified nucleotides, optimization of the delivery system, evaluation of immune effects, safety assessment, etc. The production process of mRNA vaccines mainly includes three parts: preparation of the pDNA template, production of the mRNA stock solution, loading of the delivery vector, and filling of the preparation. Compared with traditional vaccines, mRNA vaccines use a DNA template and carry out a cell-free enzymatic transcription reaction. This production process is relatively simple and can achieve rapid mass production.
[0005] Currently, in the process of preparing the RNA stock solution in the mRNA vaccine factories that have been developed and put into use internationally, since enzymes are needed to assist in gene editing, and the human body (including the oral cavity, skin, etc.) releases a large amount of enzymes in real time. Once human enzymes enter the production environment, they will disrupt gene editing, resulting in the failure of drug R & D or production. Therefore, usually, operators wear protective clothing with hoods for drug production (here, wearing protective clothing with hoods is not for isolating viruses, and mRNA production does not require a biosafety protection environment). Wearing protective clothing will affect the normal production activities of operators, have an impact on some delicate actions in drug production, and affect the drug production speed. Therefore, it is crucial to conveniently create a clean environment without enzymes and bacteria for the production of such gene editing products. Summary of the Utility Model
[0006] In view of this, the embodiment of the utility model provides a clean room without enzymes and bacteria to solve the problem that the current method of creating a clean environment without enzymes and bacteria for medicine is not conducive to drug production.
[0007] The first aspect of the embodiment of the utility model provides a clean room without enzymes and bacteria, including: a clean area without enzymes and bacteria, a one-way access personnel flow area, and a one-way access logistics area.
[0008] The flow area and the enzyme-free and aseptic clean area are separated by an operable transparent barrier system;
[0009] The logistics area and the enzyme-free and aseptic clean area are separated by a partition with a transfer door;
[0010] Purification air-conditioning systems are respectively arranged in the enzyme-free and aseptic clean area, the flow area and the logistics area, and the indoor pressure controlled by the purification air-conditioning system in the enzyme-free and aseptic clean area is higher than the indoor pressure controlled by the purification air-conditioning systems in the flow area and the logistics area by a set value.
[0011] In a possible implementation manner, the purification air-conditioning system at least includes a medium-efficiency filter.
[0012] In a possible implementation manner, the value range of the set value is 10 Pa to 15 Pa.
[0013] In a possible implementation manner, the direction between the flow area and the logistics area is defined as the target direction, and the width of the enzyme-free and aseptic clean area in the target direction is 800 mm to 1000 mm.
[0014] In a possible implementation manner, the operable transparent barrier system includes: a transparent barrier, a fixing part and operable gloves;
[0015] The transparent barrier has at least one operation opening, which is configured to separate the flow area and the enzyme-free and aseptic clean area;
[0016] The number of the operable gloves corresponds to the number of the operation openings, and each operable glove is hermetically fixed on one operation opening through the fixing part.
[0017] In a possible implementation manner, the transparent barrier is at least one of a glass barrier, an ABS board or a PVC board.
[0018] In a possible implementation manner, the operable gloves are latex gloves or rubber gloves.
[0019] The beneficial effects of the embodiments of the present utility model compared with the prior art are as follows: By setting up an enzyme-free and sterile clean area, a one-way access personnel flow area, and a one-way access material flow area, and using an operable transparent barrier system to separate the personnel flow area from the enzyme-free and sterile clean area, and using a partition with a transfer door to separate the material flow area from the enzyme-free and sterile clean area. Then, purification air conditioning systems are respectively set up in the enzyme-free and sterile clean area, the personnel flow area, and the material flow area, and the indoor pressure controlled by the purification air conditioning system in the enzyme-free and sterile clean area is set higher than the indoor pressure controlled by the purification air conditioning systems in the personnel flow area and the material flow area by a set value. Thus, by means of the one-way access personnel flow area and material flow area and the control of the indoor pressure in the enzyme-free and sterile clean area, the personnel flow area, and the material flow area, the enzyme-free and sterile clean area can well maintain an enzyme-free and sterile environment, and the operable transparent barrier system enables the operators in the personnel flow area to facilitate the operation of drug production, thereby avoiding the influence of the operators wearing hooded protective clothing on the drug production speed. BRIEF DESCRIPTION OF THE DRAWINGS
[0020] In order to more clearly illustrate the technical solutions in the embodiments of the present utility model, the following will briefly introduce the drawings required for use in the embodiments or the description of the prior art. Obviously, the following drawings are only some embodiments of the present utility model. For those of ordinary skill in the art, without creative efforts, other drawings can also be obtained based on these drawings.
[0021] Figure 1 is a schematic structural diagram of an enzyme-free and sterile clean room provided by an embodiment of the present utility model;
[0022] Figure 2 is a sectional view between the personnel flow area and the enzyme-free and sterile clean area provided by an embodiment of the present utility model;
[0023] Figure 3 is a schematic side view structural diagram of an enzyme-free and sterile clean room provided by an embodiment of the present utility model;
[0024] Figure 4 is a schematic diagram of the purification air conditioning system in an enzyme-free and sterile clean room provided by an embodiment of the present utility model;
[0025] Figure 5 is a schematic diagram of the indoor pressure of each area in an enzyme-free and sterile clean room provided by an embodiment of the present utility model;
[0026] Figure 6 is a schematic structural diagram of the purification air conditioning system provided by an embodiment of the present utility model. DETAILED DESCRIPTION OF THE EMBODIMENTS
[0027] In the following description, specific details such as specific system structures and technologies are presented for the purpose of illustration rather than limitation, so as to thoroughly understand the embodiments of the present utility model. However, those skilled in the art should clearly understand that the present utility model can also be implemented in other embodiments without these specific details. In other cases, detailed descriptions of well-known systems, devices, circuits, and methods are omitted to avoid unnecessary details from interfering with the description of the present utility model.
[0028] In order to illustrate the technical solutions described in the present utility model, the following will be described through specific embodiments.
[0029] As Figures 1-3 shown, an enzyme-free and sterile cleanroom provided by an embodiment of the present utility model includes: an enzyme-free and sterile clean area, a one-way access personnel flow area, and a one-way access material flow area.
[0030] Among them, the personnel flow area and the enzyme-free and sterile clean area are separated by an operable transparent barrier system, and the material flow area and the enzyme-free and sterile clean area are separated by a partition with a transfer door.
[0031] Purification air conditioning systems are respectively arranged in the enzyme-free and sterile clean area, the personnel flow area, and the material flow area, and the indoor pressure controlled by the purification air conditioning system in the enzyme-free and sterile clean area is higher than the set value of the indoor pressure controlled by the purification air conditioning systems in the personnel flow area and the material flow area.
[0032] As Figure 1 shown, in this embodiment, in order to create a good enzyme-free and sterile environment, unidirectional flow technology is adopted to divide the process plane of the enzyme-free and sterile cleanroom into three parts, set unidirectional flow with separate personnel flow and material flow, add a separate access channel for personnel to enter and a separate access and exit channel for materials, so as to form a personnel flow area, a material flow area, and an enzyme-free and sterile clean area.
[0033] On this basis, as Figure 4 shown, three sets of independent purification air conditioning systems are adopted in the personnel flow area, the material flow area, and the enzyme-free and sterile clean area to separate personnel, the production area, and the material flow area, avoiding enzyme cross-contamination. Exemplarily, AHU-1 is the purification air conditioning system for the material flow area, AHU-2 is the purification air conditioning system for the enzyme-free and sterile clean area, and AH-3 is the purification air conditioning system for the personnel flow area.
[0034] On this basis, as Figure 5 shown, in order to ensure that the enzyme-free and sterile environment is not contaminated by personnel all the time, pressure gradient control is carried out by using the respective purification air conditioning systems in the personnel flow area, the material flow area, and the enzyme-free and sterile clean area, and the indoor pressure of the enzyme-free and sterile clean area is set higher than the indoor pressure of the personnel flow area and the material flow area by a set value, so as to use the positive pressure bubble isolation principle to block the leakage of enzymes in the personnel activity area to the enzyme-free and sterile clean area.
[0035] Optionally, the value range of the set value can be 10 Pa to 15 Pa. Exemplarily, the set value can be 10 Pa.
[0036] In the embodiment of the present utility model, by setting an enzyme-free and sterile clean area, a unidirectional access personnel flow area, and a unidirectional access material flow area, and using an operable transparent barrier system to separate the personnel flow area from the enzyme-free and sterile clean area, and using a partition with a transfer door to separate the material flow area from the enzyme-free and sterile clean area, and then respectively setting a purification air conditioning system in the enzyme-free and sterile clean area, the personnel flow area, and the material flow area, and making the indoor pressure controlled by the purification air conditioning system in the enzyme-free and sterile clean area higher than the set value of the indoor pressure controlled by the purification air conditioning systems in the personnel flow area and the material flow area. Thus, by using the unidirectional access personnel flow area and material flow area and the control of the indoor pressure in the enzyme-free and sterile clean area, the personnel flow area, and the material flow area, the enzyme-free and sterile clean area can well maintain an enzyme-free and sterile environment, obtaining a continuous and stable enzyme-free and sterile clean production environment for future research and production of synthetic biology, gene technology, nucleic acid drugs, mRNA drugs, gene vaccines, etc. And by using the operable transparent barrier system, the operators located in the personnel flow area are convenient for drug production operations, thus avoiding the influence of the operators wearing hooded protective clothing on the drug production speed.
[0037] Optionally, in order to facilitate the operation of the operators in the personnel flow area through the operable transparent barrier system, as Figure 1 shown, the direction between the personnel flow area and the material flow area can be defined as the target direction, and the width of the enzyme-free and sterile clean area in the target direction is 800 mm to 1000 mm.
[0038] Exemplarily, in combination with Figure 3 shown, the width of the enzyme-free and sterile clean area in the target direction can be 800 mm, so as to set an operating table with a width of 400 mm to 450 mm in the target direction in the enzyme-free and sterile clean area, and set a robotic arm between the operating table and the partition of the enzyme-free and sterile clean area, so as to facilitate the transfer of the products produced in the enzyme-free and sterile clean area to the material flow area through the robotic arm.
[0039] Exemplarily, the width of the operating table in the target direction can also be similar to the width of the enzyme-free and sterile clean area in the target direction, so as to set a robotic arm on the operating table to transfer the products produced in the enzyme-free and sterile clean area to the material flow area through the robotic arm on the operating table. This embodiment does not limit this.
[0040] Optionally, in combination with Figure 2 and Figure 3 shown, for the convenience of operation, the operable transparent barrier system can include: a transparent barrier, a fixing part, and an operable glove.
[0041] The transparent barrier has at least one operation port and is configured to separate the personnel flow area from the enzyme-free and sterile clean area.
[0042] The number of operable gloves corresponds to the number of operation ports, and each operable glove is hermetically fixed to an operation port through a fixing part.
[0043] In this embodiment, the enzyme-free and sterile clean area is isolated from the personnel flow area and the logistics area by a barrier system. Exemplarily, as Figure 3 shown, the partition between the enzyme-free and sterile clean area and the logistics area can be a glass partition with a robotic arm transfer door, and the operable transparent barrier system between the enzyme-free and sterile clean area and the personnel flow area can be a barrier system composed of a transparent barrier, a fixing part, and operable gloves.
[0044] Exemplarily, the transparent barrier can be made of a transparent material with a supporting function, such as at least one of a glass barrier, an ABS board, or a PVC board. The operable gloves can be sterile isolation gloves, such as latex gloves or rubber gloves.
[0045] Optionally, as shown in Figure 6 , the purification air-conditioning system can at least include a medium-efficiency filter (i.e., the medium-efficiency filtration fan box in Figure 6 ) to meet the purification requirements of the personnel flow area, the logistics area, and the enzyme-free and sterile clean area.
[0046] As Figure 6 shown, the purification air-conditioning system (i.e., the combined air handling unit AHU-105) can be set to 5 state modes, namely normal operation, disinfection operation, disinfection exhaust, duty operation, and shutdown. Different state mode conversions can be achieved on the control cabinet and the upper computer. According to actual needs, different state mode conversions can be preferentially achieved on the control cabinet. In the figure, SA represents supply air, RA represents return air, EA represents room exhaust air, OA represents fresh air, and the air volume unit is mΦ3Φ / h.
[0047] Among them, the air handling unit fan can be equipped with a frequency converter FM, and the working state of the frequency converter is adjusted according to the static pressure sensor on the main air supply pipe to make the air supply volume reach the set value.
[0048] During normal operation:
[0049] a: Air volume control: The working state of the frequency converter is adjusted according to the static pressure sensor on the main air supply pipe to make the air supply volume reach the set value.
[0050] b: Temperature and humidity control: The valve openings of the chilled water pipeline, the hot water pipeline, and the steam humidification pipeline are adjusted to achieve constant temperature and humidity control of the return air (the temperature and humidity parameters are adjustable). If the indoor temperature is too low due to humidity control, the valve opening of the reheater coil is adjusted to control the indoor temperature. Exemplarily, the indoor temperature and humidity are set as follows: Summer: 22 ± 2°C, 55 ± 5%; Winter: 22 ± 2°C, 50 ± 5%.
[0051] c: Electric damper control: The fresh air electric valve ED105-01, the return air electric valve MD105-01, and the exhaust air electric valve MD105-03 are opened, and the disinfection exhaust air electric valve MD105-02 is closed.
[0052] d: Equipment start / stop control: The air conditioning unit and the exhaust fan unit EU105-01 are operating normally, and the disinfection exhaust fan unit EU105-02 is closed.
[0053] During disinfection operation: The disinfection method is determined according to the requirements of the owner.
[0054] a: Air volume control: Adjust the working state of the frequency converter according to the static pressure sensor on the main air supply pipe to make the air supply volume reach 1 / 2 of the design value (parameters are adjustable).
[0055] b: Temperature and humidity control: Adjust the valve openings of the chilled water pipeline, the hot water pipeline, and the steam humidification pipeline to achieve constant temperature and humidity control of the return air (temperature and humidity parameters are adjustable). If the indoor temperature is too low due to humidity control, adjust the valve opening of the reheater coil to control the indoor temperature.
[0056] c: Electric damper control: The opening degree of the fresh air electric valve VAV105-02 is 1 / 10 (parameters are adjustable), the return air electric valve MD105-01 and the exhaust air electric valve MD105-04 are opened, and the exhaust air electric valve MD105-03 and the disinfection exhaust air electric valve MD105-02 are closed.
[0057] d: Equipment start / stop control: The air conditioning unit operates with frequency conversion, the exhaust fan unit EU105-01 and the disinfection exhaust fan unit EU105-02 are closed, and disinfection steam is released into the system.
[0058] e: When the concentration of the disinfection steam reaches the specified concentration and is maintained for a certain period of time, the disinfection unit is closed. The disinfection time is determined according to the verification.
[0059] During disinfection exhaust operation: The exhaust time is determined according to the verification.
[0060] a: Air volume control: Adjust the working state of the frequency converter according to the static pressure sensor on the main air supply pipe to make the air supply volume reach 1 / 2 of the design value (parameters are adjustable).
[0061] b: Temperature and humidity control: Adjust the valve openings of the chilled water pipeline, the hot water pipeline, and the steam humidification pipeline to achieve constant temperature and humidity control of the return air (temperature and humidity parameters are adjustable). If the indoor temperature is too low due to humidity control, adjust the valve opening of the reheater coil to control the indoor temperature.
[0062] c: Electric air valve control: The fresh air electric valve ED105-01 is fully open, the fresh air electric valve VAV101-02 is opened to an opening degree of 50% fresh air ratio, the disinfection exhaust air electric valve MD105-02 and the exhaust air electric valve MD105-03 are opened, and the exhaust air electric valve MD105-04 and the return air electric valve MD105-01 are closed.
[0063] d: Equipment start-stop control: The air conditioning unit operates with frequency conversion, the exhaust fan unit EU105-01 and the disinfection exhaust fan unit EU105-02 operate normally, and the disinfection unit is closed.
[0064] During duty operation:
[0065] a: Air volume control: Adjust the working state of the frequency converter according to the static pressure sensor on the main air supply pipe to make the air supply volume reach 1 / 2 of the design value (parameters are adjustable).
[0066] b: Temperature and humidity control: Adjust the valve opening degrees of the chilled water pipeline, hot water pipeline and steam humidification pipeline to achieve constant temperature and humidity control of the return air (temperature and humidity parameters are adjustable). If the indoor temperature is too low due to humidity control, adjust the valve opening degree of the reheater coil to control the indoor temperature.
[0067] c: Electric air valve control: The opening degree of the fresh air electric valve VAV105-02 is 1 / 10 (parameters are adjustable), the return air electric valve MD105-01 and the exhaust air electric valve MD105-04 are opened, and the exhaust air electric valve MD105-03 and the disinfection exhaust air electric valve MD105-02 are closed.
[0068] d: Equipment start-stop control: The air conditioning unit operates with frequency conversion, the exhaust fan unit EU105-01 and the disinfection exhaust fan unit EU105-02 are closed, and the disinfection unit is closed.
[0069] When shutting down: All exhaust fans corresponding to this air conditioning unit are shut down; all electric and manual valves on the chilled water pipeline, steam pipeline and air duct corresponding to this air conditioning unit are closed.
[0070] Exemplarily, a fan interlock can be set. When starting up, start the supply fan first and then the exhaust fan; conversely, when shutting down, shut down the exhaust fan first and then the supply fan.
[0071] In the air conditioning unit, a primary filter, a medium-efficiency filter, a high-efficiency filter, etc. can be sequentially arranged in the direction of air flow. A differential pressure display device can be set for each stage of the filter, and a differential pressure abnormal alarm can be set for the fan. Exemplarily, when a primary filter, a medium-efficiency filter and a high-efficiency filter are set in the air conditioning unit, the pressure values of each stage of the filter can be: primary filter: 100 Pa, medium-efficiency filter: 160 Pa, high-efficiency filter: 450 Pa.
[0072] Exemplarily, a differential pressure gauge can be installed locally in a room with a pressure difference, and the readings can be manually recorded by personnel. Additionally, a differential pressure remote transmission display can be selected for one of the high-efficiency air outlets.
[0073] Exemplarily, a temperature and humidity display instrument can be installed near an exhaust air outlet or a return air outlet in a purification room (such as an enzyme-free and sterile clean area), and the temperature and humidity can be manually recorded by personnel.
[0074] In Figure 6 the position marked "70°C", a fire damper can be installed. The fire damper can be configured to output an electrical signal to the fire control center when it operates. After confirming a fire, all air conditioning and ventilation equipment within the air conditioning system interlocked with it can be shut down by the fire control center to ensure safety.
[0075] Exemplarily, an automatic air vent valve DN20 can be added on-site at the highest point or the climbing point of the air conditioning water pipe, and a drain valve DN25 can be installed at the lowest point.
[0076] For ease of control, temperature, humidity, and pressure remote detection and alarm can also be set up in key rooms (such as the personnel flow area, the logistics area, and the enzyme-free and sterile clean area). At the same time, the room pressure signal (i.e., the indoor pressure) can be provided to the variable air volume valve controller for indoor pressure control.
[0077] The above-described embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit them. Although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that they can still modify the technical solutions described in the foregoing embodiments or perform equivalent replacements for some of the technical features. These modifications or replacements do not cause the essence of the corresponding technical solutions to deviate from the spirit and scope of the technical solutions of the embodiments of the present invention and should all be included within the protection scope of the present invention.
Claims
1. A non-enzymatic and sterile clean room, characterized in that, Including: An enzyme-free and sterile clean area, a one-way access personnel flow area, and a one-way access material flow area; The personnel flow area and the enzyme-free and sterile clean area are separated by an operable transparent barrier system; The material flow area and the enzyme-free and sterile clean area are separated by a partition with a transfer door; Purification air conditioning systems are respectively provided in the enzyme-free and sterile clean area, the personnel flow area, and the material flow area, and the indoor pressure controlled by the purification air conditioning system in the enzyme-free and sterile clean area is higher than the set value than the indoor pressure controlled by the purification air conditioning systems in the personnel flow area and the material flow area; The operable transparent barrier system includes: a transparent barrier, a fixing part, and operable gloves; The transparent barrier has at least one operation port and is configured to separate the personnel flow area and the enzyme-free and sterile clean area; The number of the operable gloves corresponds to the number of the operation ports, and each operable glove is hermetically fixed on one operation port through the fixing part.
2. The enzyme-free and sterile clean room according to claim 1, characterized in that, The purification air conditioning system includes at least a medium-efficiency filter.
3. The enzyme-free and sterile clean room according to claim 1, wherein The value range of the set value is 10 Pa to 15 Pa.
4. The enzyme-free and sterile clean room according to claim 1, characterized in that, Defining the direction between the personnel flow area and the material flow area as the target direction, the width of the enzyme-free and sterile clean area in the target direction is 800 mm to 1000 mm.
5. The enzyme-free and sterile clean room according to claim 1, wherein The transparent barrier is at least one of a glass barrier, an ABS board, or a PVC board.
6. The enzyme-free and sterile clean room according to claim 1, characterized in that, The operable gloves are latex gloves or rubber gloves.