A single-use container suitable for a freeze-drying process and a freeze-drying method thereof

Abstract

The present application relates to the freeze-drying technical field, especially to a disposable container suitable for freeze-drying process and a freeze-drying method thereof.The disposable container suitable for freeze-drying process comprises a flexible container;the flexible container is a bag structure with a bacteria barrier function;the flexible container forms a liquid loading area for maintaining the geometry of the liquid by setting a frame structure;the flexible container has a first transmission interface for transmitting liquid to the inside of the container and maintaining sterility;the flexible container has a second transmission interface for transmitting powder to the outside of the container and maintaining sterility.The present application is a pre-sterilized fully-closed container applied to tray freeze-drying process, which can keep each process link of tray freeze-drying sterile without the protection of a hundred-level environment.The product of the present application can be pre-sterilized, and can be used immediately after being unpacked, so that the status confirmation of isolator and the online cleaning and sterilization of equipment in the traditional production process are no longer needed, and the production efficiency is improved.

Description

Technical Field

[0001] This invention relates to the field of freeze-drying technology, and in particular to a disposable container suitable for freeze-drying processes and a freeze-drying method thereof. Background Technology

[0002] Freeze-drying, also known as vacuum freeze-drying, is a low-temperature dehydration process. The liquid material is frozen at a low temperature, then the pressure is reduced, and water is removed through sublimation. Compared to other drying technologies, freeze-drying is biologically and chemically inert, which helps maintain drug activity. Freeze-dried drugs are porous, can be stored stably for extended periods, and are easily rehydrated to restore their activity. Therefore, freeze-drying technology is widely used in biological products, chemicals, pharmaceuticals, traditional Chinese medicine, and health products.

[0003] In pharmaceutical manufacturing, lyophilization is categorized into formulation lyophilization and active pharmaceutical ingredient (API) or intermediate lyophilization, depending on the product's application. Formulation lyophilization involves filling vials with the drug solution and then feeding them, along with the vials, into a lyophilizer. After lyophilization, the vials are capped to produce the finished drug product. However, APIs or intermediates cannot be used directly as drugs after lyophilization; therefore, their lyophilization process is not completed in vials. Instead, a tray is typically used to hold the drug solution for lyophilization, followed by powder collection and subsequent post-processing. This patent primarily focuses on optimizing the tray lyophilization process.

[0004] In traditional tray freeze-drying processes, stainless steel trays are often used to hold the pharmaceutical solution due to their low cost, reusability, and lack of reaction with the solution. However, GMP regulations require that pharmaceutical production processes minimize contamination risks and reduce human intervention. Therefore, in traditional stainless steel tray freeze-drying processes, both the pharmaceutical solution and the freeze-dried powder require Class 100 environmental protection. The process typically includes: cleaning the trays, transferring them to a sterilizer, transferring the sterilized trays to an isolator, adding liquid to the trays under the isolator's protection and transferring them to the freeze dryer, removing the freeze-dried trays under the isolator's protection and collecting the powder, and temporarily storing the collected powder trays in the isolator until the batch production is complete.

[0005] Despite the advantages of stainless steel trays, they are prone to powder adhesion, leading to reduced powder yield. Furthermore, metal powder can easily be mixed in during powder collection. Additionally, the large temperature fluctuations during freeze-drying can cause variations in the flatness of the tray bottom, affecting freeze-drying quality. Therefore, freeze-drying membrane technology has been developed to address these issues. A freeze-drying membrane consists of a low-temperature resistant membrane material that does not affect drug quality, fixed to a frame to form a disc-shaped container for freeze-drying the drug solution. Because the low-temperature resistant membrane material is less prone to deformation under temperature changes during freeze-drying, the consistency of the freeze-drying process is optimized. Simultaneously, the high surface smoothness of the membrane material reduces powder adhesion, improving powder yield.

[0006] Initially, the use of freeze-drying membranes required manual fixing of the membrane to the frame, which was labor-intensive. Based on this, disposable plastic freeze-drying trays were developed, where the membrane was directly welded to a plastic frame. However, due to factors such as the softness of the base membrane, the low strength of the plastic tray, and the inconvenience of handling within the isolator, this solution has been difficult to widely adopt on production lines at a manufacturing level.

[0007] In recent years, a type of sealed freeze-drying box has appeared on the market. Based on a freeze-drying membrane as the bottom film and a plastic frame, a waterproof and breathable membrane is welded to the top of the tray, and a liquid injection port is provided. Examples include the disposable freeze-drying box from Gore, Inc. This type of freeze-drying box is manufactured and pre-sterilized in a clean environment. When in use, the liquid is injected into a Class 100 environment and the lid is tightened, forming a sealed space that effectively prevents liquid spillage during transport and protects operators. After freeze-drying, the bottom membrane is cut open to collect the powder. Therefore, using freeze-drying boxes eliminates the need for cleaning and sterilization functions for freeze-drying trays in the freeze-drying production line. Although the box is sealed during freeze-drying, considering that the bottom membrane needs to be opened for powder collection, regulations require completion in a Class 100 environment. Therefore, the freeze-drying process still needs to be completed in a Class 100 environment to avoid transferring the freeze-dried powder from a low-cleanliness environment to a high-cleanliness environment.

[0008] In summary, current market-available tray freeze-drying solutions all require at least isolators to ensure pharmaceutical production in a Class 100 environment. The most widely used stainless steel trays necessitate additional tray cleaning, sterilization, and transfer capabilities, and the freeze-drying equipment must also have online cleaning and sterilization functions to prevent contamination of the pharmaceuticals during the freeze-drying process.

[0009] The information disclosed in this background section is intended only to enhance the understanding of the general background of the invention and should not be construed as an admission or in any way implying that the information constitutes prior art known to those skilled in the art. Summary of the Invention

[0010] The purpose of this invention is to provide a disposable container suitable for freeze-drying processes, so as to solve the technical problems existing in the prior art.

[0011] To achieve the above objectives, the present invention adopts the following technical solution: This invention provides a disposable container suitable for freeze-drying processes, comprising: a flexible container; The flexible container is a bag structure with a bacterial barrier function. The flexible container forms a liquid loading area that maintains the geometry of the liquid by setting a frame structure; The flexible container has a first transfer interface for transferring liquid into its interior while maintaining sterility. The flexible container has a second transfer interface for conveying powder to its exterior while maintaining sterility.

[0012] Preferably, the flexible container is constructed by splicing together several membrane materials; at least one membrane material is a breathable membrane with antibacterial function.

[0013] Preferably, the bottom membrane of the flexible container is made of PP or PE membrane; the top membrane of the flexible container is made of PE spun film or expanded polytetrafluoroethylene film.

[0014] Preferably, the frame structure is a built-in frame; The built-in frame is located inside the flexible container; The built-in frame is connected to the inner surface of the bottom membrane of the flexible container, and the two together form a liquid loading area with an open top.

[0015] Preferably, the top of the built-in frame is provided with several reinforcing ribs.

[0016] Preferably, the material of the built-in frame is polyethylene or polypropylene.

[0017] Preferably, the frame structure is an external frame; The external frame is located outside the flexible container; The external frame is connected to the outer surface of the bottom membrane of the flexible container, and the two together form a tray-shaped liquid loading area.

[0018] Preferably, the external frame is a tray-shaped structure, and a support is welded to the inner surface of the bottom membrane of the flexible container. The external frame and the support are connected by a coupling and fixing structure.

[0019] Preferably, magnets are provided at the four corners of the external frame; magnets are provided inside the legs of the bracket; and a cross-shaped reinforcing rib is provided at the top of the bracket.

[0020] Preferably, the first transmission interface is disposed on the top membrane of the flexible container; the first transmission interface is a cryogenic flexible tube for aseptic connection and aseptic disconnection.

[0021] Preferably, the second transmission interface is disposed on the bottom membrane of the flexible container; the first transmission interface adopts the passive door form in a dual-door system.

[0022] The present invention also provides a freeze-drying method, which uses the disposable container suitable for freeze-drying process, and includes the following steps: Place the flexible container in a freeze dryer; The freeze-dried liquid is added into the flexible container through the first transfer interface using aseptic connection technology. After the filling is completed, the first transfer interface is sealed using aseptic disconnection technology. Start the freeze dryer to perform freeze drying; After freeze-drying is complete, the flexible container is removed, and the freeze-dried powder is aseptically transferred to the powder equipment via the second transfer interface.

[0023] By adopting the above technical solution, the present invention has the following beneficial effects: The disposable container provided by this invention, suitable for freeze-drying processes, serves as a pre-sterilized, fully enclosed container for tray freeze-drying, enabling each step of the tray freeze-drying process to remain sterile even without Class 100 environmental protection. Therefore, freeze-drying production lines no longer require cleaning equipment, sterilization equipment, or isolators. Furthermore, freeze-drying equipment no longer needs online cleaning and sterilization functions, significantly reducing production line investment and shortening the production line validation cycle, thus accelerating production. Simultaneously, the product of this invention can be pre-sterilized and used immediately after disassembly. The status verification of isolators and the online cleaning and sterilization of equipment in traditional production processes are no longer necessary, improving production efficiency. Attached Figure Description

[0024] To more clearly illustrate the specific embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the specific embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are some embodiments of the present invention. For those skilled in the art, other drawings can be obtained from these drawings without creative effort.

[0025] Figure 1 A perspective view of a disposable container suitable for freeze-drying process provided in Embodiment 1 of the present invention; Figure 2 for Figure 1 A side view of a disposable container suitable for freeze-drying process is shown. Figure 3 A perspective view of a disposable container suitable for freeze-drying process provided in Embodiment 2 of the present invention; Figure 4 for Figure 3 A side view of a disposable container suitable for freeze-drying process is shown. Figure 5 This is a schematic diagram of the structure of the bottom membrane provided in Embodiment 2 of the present invention; Figure 6 This is a schematic diagram of the external frame provided in Embodiment 2 of the present invention; Figure 7 This is a schematic diagram of a passive door provided in Embodiment 2 of the present invention; Figure 8 This is a cross-sectional view of a disposable container suitable for freeze-drying process provided in Embodiment 2 of the present invention.

[0026] Icons: 1-Low temperature resistant hose; 2-External frame; 3-Top membrane; 4-Bracket; 5-Passive door; 6-Bottom membrane; 7-Internal frame; 8-Magnet. Detailed Implementation

[0027] The technical solution of the present invention will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0028] The specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings. It should be understood that the specific embodiments described herein are for illustration and explanation only and are not intended to limit the present invention. Example

[0029] This embodiment provides a disposable container suitable for freeze-drying processes, comprising: a flexible container; the flexible container is a bag structure with a bacterial barrier function; the flexible container forms a liquid loading area that maintains the geometry of the liquid by setting a frame structure, in this embodiment, the frame structure is an internal frame 7; the internal frame 7 is located inside the flexible container; the internal frame 7 is connected to the inner surface of the bottom membrane 6 of the flexible container, and the two together form a top-open liquid loading area. The flexible container has a first transfer interface for transferring liquid into its interior while maintaining sterility; the flexible container has a second transfer interface for transferring powder to its exterior while maintaining sterility.

[0030] In this embodiment, the antibacterial barrier can be made by splicing membrane materials into a bag shape, wherein the membrane material in contact with the freeze-drying panel is a low-temperature resistant membrane material suitable for the freeze-drying process. Many freeze-drying membranes are already commercially available and widely used, with polyethylene or polypropylene being the most common materials. Considering that the sublimated water during freeze-drying needs to permeate through the wall of the flexible container, the flexible container must contain at least a portion of antibacterial and breathable membrane material. Commercially available membrane materials include Tyvek membranes made from polyethylene spun fibers and filter membranes made from expanded polytetrafluoroethylene. With the development of disposable biopharmaceutical technology, there are many references available for splicing membrane materials into a bag shape. Two membrane materials can be welded together to form a flat bag, or several membrane materials can be spliced ​​together to form a three-dimensional bag. Considering the heat transfer requirements of the liquid during freeze-drying, the liquid level is usually not too high, meaning the vertical dimensions of the bag are not critical. Therefore, preferably, the overall structure of the bag can be a flat bag made by welding two membrane materials together. The bottom, in contact with the freeze-drying panel, can use a commercially available freeze-drying membrane. The top membrane material is wholly or partially made of antibacterial and breathable membrane material for the permeation of sublimated water. Preferably, commercially available PE spun membrane (Tyvek membrane) or expanded polytetrafluoroethylene membrane (ePTFE membrane) can be used, depending on the compatibility of the feed liquid.

[0031] In this embodiment, in the case where the built-in frame 7 is used to form the liquid loading area, the liquid loading area can be formed by the built-in frame 7 and the bottom membrane 6 together. The frame ensures that the bottom membrane 6 remains flat during the freeze-drying process, and together with the bottom membrane 6, forms a container space with an open top for containing the freeze-dried liquid.

[0032] In this embodiment, when the built-in frame 7 is used, several reinforcing ribs can be provided at the top of the frame to prevent the top membrane material from contacting the liquid during freeze-drying and affecting the freeze-drying quality. Alternatively, an external device can be used to fix the top membrane material. like Figures 1 to 2 As shown, the flexible container is made of two membrane materials: a bottom membrane made of polypropylene for freezing and a top membrane made of expanded polytetrafluoroethylene (ePTFE) for both antibacterial and breathable properties. The top membrane has a welded opening connected to a low-temperature resistant PVC pipe, the end of which is sealed with a plug. An internal frame 7, made of low-temperature resistant polypropylene, is welded onto the bottom membrane 6. Several reinforcing ribs are provided at the top of the internal frame 7 to prevent the top membrane from sagging and contacting the liquid during freeze-drying. A passive door 5, also made of low-temperature resistant polypropylene, is also welded onto the bottom membrane.

[0033] In this embodiment, the connection process between the built-in frame 7 and the bottom membrane 6 can be welding, gluing, bonding, mechanical connection, etc. Preferably, polyethylene or polypropylene can be selected based on the welding compatibility with the membrane material. When using the built-in frame 7, several reinforcing ribs can be provided at the top of the frame to prevent the top membrane material from contacting the liquid during freeze-drying and affecting the freeze-drying quality. Alternatively, an external device can be used to fix the top membrane material.

[0034] In this embodiment, preferably, the first transmission interface is disposed on the top membrane 3 of the flexible container; the first transmission interface is a cryogenic hose 1 for aseptic connection and aseptic disconnection. The cryogenic hose 1 is connected to the double-ended opening of the top membrane 3.

[0035] Specifically, the first transmission interface is a transmission interface capable of transferring liquid into the bag while maintaining sterility. Preferably, a commercially available, aseptically connectable and disconnectable cryogenic tubing 1 can be used. Aseptic connection technology is used to connect the container to the liquid storage container, and after liquid injection, aseptic disconnection technology is used to disconnect the container from the liquid storage container, ensuring that the liquid is not contaminated during the injection process. This tubing has been successfully applied in consumables for cryogenic storage, freeze-thaw processes, etc. Preferably, the material is made of PVC.

[0036] In this embodiment, preferably, the second transmission interface is disposed on the bottom membrane 6 of the flexible container; the first transmission interface adopts the passive door 5 form of a dual-door system. Specifically, the dual-door system is also known in the industry as an α-β door system or an AB door system (e.g., the DPTE system from Geting Corporation). When so named, the passive door 5 is also called a β door or a B door. Dual-door systems are widely used in the cross-level transportation of materials in the fields of medical, biological, pharmaceutical, chemical, and nuclear power. It is a proven system that can effectively prevent the exchange between the contents and the environment during transportation, playing a role in preventing contamination or protecting users. With years of development, the structure of the passive door 5 in the dual-door system is a mature and publicly disclosed technology, which includes at least a door plate with a flange for engaging with the active door to open the passive door 5. It includes at least one valve body, which is connected to a container by welding or mechanical connection. In this patent, the container is connected to the flexible bag body. It includes at least one sealing ring to ensure the sealing performance between the door plate and the valve body, and to ensure the sealing performance after docking with the active door. However, the application of dual-door systems in the pharmaceutical industry is mainly in environments requiring ambient temperature or high-temperature, moist heat sterilization. Therefore, the material for the passive door 5 is primarily chosen to be suitable for both ambient and high-temperature environments, such as polycarbonate and stainless steel. Since the process used in this invention is freeze-drying, the material selection for the passive door 5 primarily considers low-temperature resistance. For single-use applications, polypropylene is preferably used, as it is widely used in cryogenic storage consumables. Polysulfone and other plastics are also known to be suitable for low-temperature environments; however, they are more expensive. Furthermore, in some scenarios, stainless steel can be used to make the valve body, which is mechanically connected to the bag body. In this case, only the bag body is for single use, while the stainless steel valve body can be reused.

[0037] In this invention, the passive door 5 serves as a window for material transfer. During the liquid injection stage, the active door can be opened to allow liquid to be added into the frame. After freeze-drying, the passive door 5 can be opened with the active door to aseptically transfer the freeze-dried powder to the powder processing equipment.

[0038] Although using a passive door 5 for liquid addition is feasible and proven, its operation is relatively complex. Therefore, the aseptic transfer interface for the liquid described in this invention can be achieved by welding a bag opening to the bag body to connect the tubing. Using commercially available aseptic connectors or aseptic connection machines, the connection to the storage container is made to add the liquid. After addition, the container can be resealed using aseptic disconnection technology. The aforementioned aseptic connection and disconnection technologies are mature technologies in the industry, and many manufacturers provide corresponding equipment and consumables. These will not be detailed further in this invention. When using tubing for liquid addition, tubing capable of withstanding freeze-drying processes must be used. Preferably, low-temperature resistant tubing made of PVC material can be used, which has been successfully applied in cell cryopreservation, freeze-thaw processes, and other similar procedures.

[0039] The working principle of this embodiment is as follows: This container is manufactured in a clean environment and sterilized beforehand using gamma rays. Users can use it simply by opening the packaging. Specific operating steps are as follows: (1) After unpacking, place the container directly on the freeze dryer panel. Since the container is a clean and sterilized closed system, this process does not require Class 100 environmental protection, and the freeze dryer does not need to be cleaned or sterilized online. (2) Connect the storage container using a verified pipe fitting machine. Use a peristaltic pump to add liquid into the frame inside the container.

[0040] (3) After filling to the required volume, disconnect the injection line using a sterile disconnector, at which point the line is resealed. Therefore, Class 100 environmental protection is no longer required during the injection process. (4) Close the freeze dryer door and begin the freeze drying process. Because the container is a completely closed system, only sublimated water is allowed to pass through. Therefore, drug contamination can be effectively prevented during this process.

[0041] (5) After freeze-drying is complete, remove the container and carefully transfer it to the powder equipment.

[0042] (6) Connect the passive door 5 on the container to the active door on the powder collection device, and open the active door.

[0043] (7) Carefully transfer the powder from the container into the powder collection device.

[0044] (8) After the powder is collected, close the active door. Since the powder transfer uses an industry-proven and mature system, this process does not require Class 100 environmental protection. The freeze-drying process is now complete. Example

[0045] like Figures 3 to 8 As shown, this second embodiment is a further modification of the first embodiment. This second embodiment includes the technical content disclosed in the first embodiment. The technical content that is the same as that in the first embodiment will not be repeated. The differences between this second embodiment and the first embodiment are described below.

[0046] This embodiment provides a disposable container suitable for freeze-drying processes, comprising: a flexible container; the flexible container is a bag structure with a bacterial barrier function; the flexible container forms a liquid loading area that maintains the geometry of the liquid by setting a frame structure. In this embodiment, preferably, the frame structure is an external frame 2; the external frame 2 is located outside the flexible container; the external frame 2 is connected to the outer surface of the bottom film 6 of the flexible container, and the two together form a tray-shaped liquid loading area. The flexible container has a first transfer interface for transferring liquid into its interior while maintaining sterility; the flexible container has a second transfer interface for transferring powder to its exterior while maintaining sterility.

[0047] In this embodiment, the antibacterial barrier can be made by splicing membrane materials into a bag shape, wherein the membrane material in contact with the freeze-drying panel is a low-temperature resistant membrane material suitable for the freeze-drying process. Many freeze-drying membranes are already commercially available and widely used, with polyethylene or polypropylene being the most common materials. Considering that the sublimated water during freeze-drying needs to permeate through the wall of the flexible container, the flexible container must contain at least a portion of antibacterial and breathable membrane material. Commercially available membrane materials include Tyvek membranes made from polyethylene spun fibers and filter membranes made from expanded polytetrafluoroethylene. With the development of disposable biopharmaceutical technology, there are many references available for splicing membrane materials into a bag shape. Two membrane materials can be welded together to form a flat bag, or several membrane materials can be spliced ​​together to form a three-dimensional bag. Considering the heat transfer requirements of the liquid during freeze-drying, the liquid level is usually not too high, meaning the vertical dimensions of the bag are not critical. Therefore, preferably, the overall structure of the bag can be a flat bag made by welding two membrane materials together. The bottom, in contact with the freeze-drying panel, can use a commercially available freeze-drying membrane. The top membrane material is wholly or partially made of antibacterial and breathable membrane material for the permeation of sublimated water. Preferably, commercially available PE spun membrane (Tyvek membrane) or expanded polytetrafluoroethylene membrane (ePTFE membrane) can be used, depending on the compatibility of the feed liquid.

[0048] Preferably, the external frame 2 is a tray-shaped structure, and magnets 8 are provided at the four corners of the external frame 2; a support 4 is welded to the inner surface of the bottom film 6 of the flexible container, and magnets 8 are provided in the legs of the support 4, and a cross reinforcing rib is provided at the top of the support 4.

[0049] Preferably, when the liquid loading area is composed of an external frame 2, the external frame 2 can be designed in the shape of a tray. Magnets 8 are provided on the tray, preferably at the four corners of the tray. A bracket 4 is welded to the bottom film 6, and magnets 8 are installed in the feet of the bracket 4. In use, the magnets 8 inside the bag are aligned with the magnets 8 on the tray to flatten the bottom film 6 and ensure uniform heat transfer.

[0050] The external frame 2 can be integrated with a freeze dryer, directly utilizing the tray-shaped freeze-drying panel as support. The integration solution between the tray and the freeze dryer can refer to commercially available flip-plate freeze dryers. When using the bag body of this invention in conjunction with a flip-plate freeze dryer, the freeze dryer no longer needs to be designed with online cleaning and online sterilization devices, and the discharging of powder becomes much easier.

[0051] During freeze-drying, it is necessary to prevent the top membrane material from sagging and contacting the liquid, which would affect the freeze-drying quality. Preferably, this can be prevented by adding several reinforcing ribs to the top of the frame or support 4. Other methods, such as using external mechanisms to fix the top membrane material or adding additional support mechanisms inside the container, are still within the scope of protection of this patent.

[0052] This container is manufactured in a clean environment and sterilized beforehand using gamma rays. Users can use it simply by opening the packaging. Specific operating steps are as follows: (1) After unpacking, place the container directly on the tray-shaped freeze-drying panel in the freeze dryer. Since the container is a clean and sterilized closed system, this process does not require Class 100 environmental protection, and the freeze dryer does not need to be cleaned or sterilized online.

[0053] (2) Connect the magnets 8 at the four corners of the bag to the magnets 8 at the four corners of the tray, and flatten the bottom film 6.

[0054] (3) Connect the storage container using a verified pipe fitting machine. Use a peristaltic pump to add liquid into the frame inside the container.

[0055] (4) After filling to the required volume, disconnect the injection line using a sterile disconnecting machine, and then reseal the line. Therefore, Class 100 environmental protection is no longer required during the injection process.

[0056] (5) Close the freeze dryer door and begin the freeze drying process. Because the container is a completely closed system, only sublimated water is allowed to pass through. Therefore, drug contamination can be effectively prevented during this process.

[0057] (6) After freeze-drying is complete, remove the container and carefully transfer it to the powder equipment.

[0058] (7) Connect the passive door 5 on the container to the active door on the powder collection device, and open the active door.

[0059] (8) Carefully transfer the powder from the container into the powder collection device.

[0060] (9) After the powder is collected, close the active door. Since the powder transfer uses an industry-proven and mature system, this process does not require Class 100 environmental protection. The freeze-drying process is now complete.

[0061] In summary, using the product described in this invention, the injection of the freeze-drying liquid employs aseptic connection and aseptic disconnection technology. During the freeze-drying process, the bag body can ensure the permeation of sublimated water while preventing contamination, and the collection of freeze-dried powder utilizes aseptic transfer technology. The entire process no longer requires Class 100 environmental protection. Therefore, isolators are no longer necessary during production. Since the containers are produced in a clean environment and sterilized by methods such as radiation, moist heat, or ethylene oxide, cleaning and sterilization equipment at the freeze-drying production site is also no longer essential. Therefore, the overall investment in the freeze-drying production line is significantly reduced. Simultaneously, due to the reduction in necessary equipment, the area of ​​the production workshop and the construction of public systems can also be reduced, further reducing the initial investment and subsequent operating costs of the production line. Furthermore, the reduction in equipment also simultaneously reduces the cycle and cost of production line validation, significantly shortening the production line's commissioning cycle. At the same time, the reduction in equipment also accelerates the efficiency of subsequent batch production, because cleaning and sterilization are no longer required during batch production, and isolator performance validation is no longer necessary; the freeze dryer also does not require online cleaning and online sterilization. In addition, when used in conjunction with a flip-plate freeze dryer, the powder discharge process can be effectively simplified.

[0062] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, and not to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some or all of the technical features; and these modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the scope of the technical solutions of the embodiments of the present invention.

Claims

1. A disposable container suitable for freeze-drying processes, characterized in that, include: Flexible containers; The flexible container is a bag structure with a bacterial barrier function. The flexible container forms a liquid loading area that maintains the geometry of the liquid by setting a frame structure; The flexible container has a first transfer interface for transferring liquid into its interior while maintaining sterility. The flexible container has a second transfer interface for conveying powder to its exterior while maintaining sterility. The frame structure is an external frame; the external frame is located outside the flexible container; the external frame is connected to the outer surface of the bottom membrane of the flexible container, and the two together form a tray-shaped liquid loading area; the external frame is a tray-shaped structure, and a support is welded to the inner surface of the bottom membrane of the flexible container, and the external frame and the support are connected by a coupling and fixing structure.

2. The disposable container suitable for freeze-drying process according to claim 1, characterized in that, The flexible container is constructed by splicing together several membrane materials; at least one membrane material is a breathable membrane with antibacterial function.

3. The disposable container suitable for freeze-drying process according to claim 1, characterized in that, The first transmission interface is disposed on the top membrane of the flexible container; the first transmission interface is a cryogenic flexible tube for aseptic connection and aseptic disconnection.

4. The disposable container suitable for freeze-drying process according to claim 1, characterized in that, The second transmission interface adopts the passive door form in a dual-door system.

5. A freeze-drying method, characterized in that, The disposable container suitable for the freeze-drying process is used as described in any one of claims 1 to 4.

6. The freeze-drying method according to claim 5, characterized in that, The steps include the following: Place the flexible container in a freeze dryer; The freeze-dried liquid is added into the flexible container through the first transfer interface using aseptic connection technology. After the filling is completed, the first transfer interface is sealed using aseptic disconnection technology. Start the freeze dryer to perform freeze drying; After freeze-drying is complete, the flexible container is removed, and the freeze-dried powder is aseptically transferred to the powder equipment via the second transfer interface.

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