Disposable container suitable for freeze-drying process and freeze-drying method thereof

Abstract

The invention relates to the technical field of freeze-drying, in particular to a disposable container suitable for a freeze-drying process and a freeze-drying method of the disposable container. The disposable container suitable for a freeze-drying process comprises: a flexible container; the flexible container is of a bag body structure with a bacterium blocking and shielding function; the flexible container is provided with a frame structure to form a liquid loading area for maintaining the geometrical shape of feed liquid; the flexible container is provided with a first transmission interface for transmitting liquid into the flexible container and keeping the liquid sterile; the flexible container has a second delivery interface that delivers the powder to the outside thereof and remains sterile. As a pre-sterilized totally-closed container applied to a tray freeze-drying process, each process link of tray freeze-drying can be kept sterile without protection of a hundred-level environment. The product provided by the invention can be sterilized in advance and can be used after being disassembled, the state confirmation of the isolator and the on-line cleaning and on-line sterilization of equipment in the traditional production process are not needed any more, and the production efficiency is improved.

Description

Technical Field

[0001] The invention relates to the technical field of freeze drying, in particular to a disposable container suitable for a freeze drying process and a freeze drying method thereof. Background Art

[0002] Freeze-drying technology, also known as vacuum freeze-drying technology, is a low-temperature dehydration process. The liquid is frozen at low temperatures, and then the pressure is reduced to remove water by sublimation. Compared with other drying technologies, the freeze-drying process is biologically and chemically inert, which is conducive to maintaining the activity of the drug. After freeze-drying, the drug is porous, can be stored stably for a long time, and can be easily rehydrated to restore activity. Therefore, freeze-drying technology is widely used in biological products, chemicals, medical drugs, Chinese herbal medicines and health products.

[0003] In drug production, according to the application of the product, it is divided into freeze drying of preparations and freeze drying of raw materials or intermediate drugs. Among them, freeze drying of preparations is to fill the liquid medicine into a vial, and then send it to the freeze dryer together with the vial for freeze drying. After freeze drying, it is capped to make a finished drug. However, the raw materials or intermediate drugs cannot be used directly as drugs after freeze drying. Therefore, the freeze drying process is not completed in the vial. Usually, the liquid medicine is loaded on a tray to complete freeze drying, and then the powder is collected and related post-processing is performed. This patent mainly focuses on the optimization of the tray freeze drying process.

[0004] In the traditional tray freeze-drying process, stainless steel trays are often used to hold the drug solution because of their low price, reusability, and no reaction with the drug solution. According to GMP regulations, the risk of contamination should be reduced as much as possible during the pharmaceutical production process, and human interference should be reduced. Therefore, in the traditional stainless steel tray freeze-drying process, both the drug solution and the freeze-dried powder require Class 100 environmental protection. The process often includes: cleaning the tray, transferring it to the sterilization cabinet, transporting the sterilized tray to the isolator, adding liquid to the tray under the protection of the isolator and transferring it to the freeze dryer, taking out the freeze-dried tray and collecting the powder under the protection of the isolator, and temporarily storing the tray with collected powder in the isolator until the batch production is completed.

[0005] Although stainless steel trays have the above advantages, they are prone to adhere to powder, resulting in a lower yield of drug powder. And metal powder is easily mixed in during the process of collecting powder. At the same time, due to the large temperature changes during the freeze-drying process, the flatness of the bottom of the tray is prone to change, which in turn affects the quality of freeze-drying. Therefore, freeze-drying membrane technology has been developed in this context. The freeze-drying membrane is a layer of low-temperature resistant film material that does not affect the quality of the drug fixed on the frame to form a disc-shaped container to load the drug solution for freeze-drying. Since the low-temperature resistant film material is not easy to deform under the temperature changes of the freeze-drying process, the consistency of the freeze-drying process is optimized. At the same time, the surface finish of the film material is high, and it is not easy to adhere to powder, which can improve the yield of drug powder.

[0006] In the early days, freeze-dried membranes needed to be manually fixed to the frame, which was labor-intensive. On this basis, disposable plastic freeze-dried trays with the membrane directly welded to the plastic frame appeared on the market. However, due to the soft bottom membrane, low strength of the plastic tray, and inconvenient operation in the isolator, this solution is difficult to be widely used on production-level production lines.

[0007] In recent years, a closed freeze-drying box has appeared on the market. On the basis of the bottom membrane being a freeze-drying film and the frame being a plastic, a layer of water-proof and breathable membrane is welded on the top of the plate, and a liquid injection port is set. For example, the disposable freeze-drying box of Gore Company in the United States. This freeze-drying box is produced in a clean environment and sterilized in advance. When used, after the liquid is injected and the lid is tightened in a Class 100 environment, the box forms a closed space, which can effectively prevent the liquid from spilling during transportation and protect the operator. After the freeze-drying is completed, the bottom membrane material is cut with a tool to complete the powder collection. Therefore, using a freeze-drying box, the freeze-drying production line no longer needs to plan the cleaning and sterilization functions of the freeze-drying plate. Although the box is sealed during the freeze-drying process, considering that the bottom membrane needs to be opened when collecting the powder, according to regulations, it needs to be completed in a Class 100 environment. Therefore, the freeze-drying process still needs to be completed in a Class 100 environment to avoid the transportation of freeze-dried drug powder from a low cleanliness environment to a high cleanliness environment.

[0008] In summary, the current tray freeze-drying solutions on the market require at least an isolator to ensure that the drugs are produced in a Class 100 environment. The most widely used stainless steel trays require additional tray cleaning, sterilization and transportation capabilities, and the freeze-drying equipment also needs to have online cleaning and online sterilization functions to avoid contamination of drugs during the freeze-drying process.

[0009] The information disclosed in this background technology section is only intended to deepen the understanding of the overall background technology of the present invention, and should not be regarded as acknowledging or suggesting in any form that the information constitutes the prior art already known to those skilled in the art. Summary of the invention

[0010] The object of the present invention is to provide a disposable container suitable for a freeze-drying process to solve the technical problems existing in the prior art.

[0011] In order to achieve the above object, the present invention adopts the following technical solutions: The present invention provides a disposable container suitable for a freeze-drying process, comprising: a flexible container; The flexible container is a bag structure with a bacteria-proof barrier function; The flexible container forms a liquid loading area that maintains the geometric shape of the liquid by providing a frame structure; The flexible container has a first transfer interface for transferring liquid into the interior thereof while maintaining sterility; The flexible container has a second transfer interface for transferring the powder to the exterior thereof while maintaining sterility.

[0012] Preferably, the flexible container is formed by splicing a plurality of membrane materials; at least one membrane material is a breathable membrane with a bacteria-blocking function.

[0013] Preferably, the bottom film of the flexible container is made of PP film or PE film; the top film 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 internal frame is connected to the inner surface of the bottom film of the flexible container, and the two together form a liquid loading area with an open top.

[0015] Preferably, a plurality of reinforcing ribs are provided on the top of the built-in frame.

[0016] Preferably, the built-in frame is made of 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 film 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, a bracket is welded on the inner surface of the bottom film of the flexible container, and the external frame and the bracket are connected via a coupling fixing structure.

[0019] Preferably, magnets are arranged at the four corners of the external frame; magnets are arranged inside the legs of the bracket, and cross reinforcing ribs are arranged on the top of the bracket.

[0020] Preferably, the first transmission interface is arranged on the top film of the flexible container; the first transmission interface is a low-temperature resistant hose used for aseptic connection and aseptic disconnection.

[0021] Preferably, the second transmission interface is arranged on the bottom film of the flexible container; and the first transmission interface adopts the form of a passive door in a double-door system.

[0022] The present invention also provides a freeze-drying method, which uses the disposable container suitable for the freeze-drying process, and comprises the following steps: placing the flexible container in a freeze dryer; The freeze-dried liquid is filled into the flexible container through the first transmission interface by using an aseptic connection technique, and after the filling is completed, the first transmission interface is sealed by using an aseptic disconnection technique; Start the freeze dryer to perform freeze drying; After freeze-drying is completed, the flexible container is taken out, and the freeze-dried powder is aseptically transferred to the powder equipment through the second transfer interface.

[0023] By adopting the above technical solution, the present invention has the following beneficial effects: The disposable container suitable for the freeze-drying process provided by the present invention is a pre-sterilized fully enclosed container used in the tray freeze-drying process, which can keep each process link of the tray freeze-drying sterile without the protection of a Class 100 environment. Therefore, the freeze-drying production line no longer needs to plan cleaning equipment, sterilization equipment and isolators, and the freeze-drying equipment no longer needs online cleaning and online sterilization functions, which can greatly reduce the production line investment and shorten the production line verification cycle, and accelerate production. At the same time, the product of the present invention can be sterilized in advance and can be disassembled and used. The status confirmation of the isolator and the online cleaning and online sterilization of the equipment in the traditional production process are no longer required, which improves production efficiency. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0025] Figure 1 A three-dimensional diagram of a disposable container suitable for a freeze-drying process provided in Example 1 of the present invention; Figure 2 for Figure 1 A side view of a disposable container suitable for a lyophilization process is shown; Figure 3 A three-dimensional diagram of a disposable container suitable for a freeze-drying process provided in the second embodiment of the present invention; Figure 4 for Figure 3 A side view of a disposable container suitable for a lyophilization process is shown; Figure 5 A schematic diagram of the structure of a base film provided in Embodiment 2 of the present invention; Figure 6 A schematic diagram of the structure of an external frame provided in Embodiment 2 of the present invention; Figure 7 A schematic diagram of a passive door provided in Embodiment 2 of the present invention; Figure 8 A cross-sectional view of a disposable container suitable for a freeze-drying process provided in Example 2 of the present invention.

[0026] Icon: 1- low temperature resistant hose; 2- bottom membrane; 3- top membrane; 4- bracket; 5- passive door; 6- bottom membrane; 7- built-in frame; 8- magnet. DETAILED DESCRIPTION

[0027] The technical solution of the present invention will be described clearly and completely below in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0028] The specific implementation of the present invention is described in detail below in conjunction with the accompanying drawings. It should be understood that the specific implementation described here is only used to illustrate and explain the present invention, and is not used to limit the present invention. Example

[0029] The first embodiment provides a disposable container suitable for freeze-drying process, which includes: a flexible container; the flexible container is a bag structure with a bacteria barrier function; the flexible container forms a liquid loading area that maintains the geometric shape of the liquid by setting a frame structure, and in this embodiment, the frame structure is a built-in frame 7; the built-in frame 7 is located inside the flexible container; the built-in frame 7 is connected to the inner surface of the bottom film 62 of the flexible container, and the two together form a liquid loading area with an open top. The flexible container has a first transmission interface for transmitting liquid to the inside and maintaining sterility; the flexible container has a second transmission interface for transmitting powder to the outside and 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. There are many freeze-dried membranes on the market that have been maturely applied, and common materials mainly use polyethylene or polypropylene. Considering that the sublimated water in the freeze-drying process needs to pass through the wall of the flexible container, the flexible container at least contains part of the antibacterial breathable membrane material. The mature membrane materials used on the market include Tyvek membrane made of polyethylene spinning and filter membrane made of expanded polytetrafluoroethylene. With the development of disposable technology for biopharmaceuticals, there are many references on the market for splicing membrane materials into bag bodies. Two pieces of membrane materials can be welded to form a flat bag body, or several pieces of membrane materials can be spliced ​​to form a three-dimensional bag body. Considering the heat transfer requirements of liquids during freeze-drying, the liquid level position is usually not too high, that is, the size requirements of the bag body in the vertical direction are not high. Therefore, preferably, the overall structure of the bag body can adopt a flat bag welded by two pieces of membrane materials. Among them, the bottom is in contact with the freeze-drying panel, and the mature freeze-drying membrane used on the market can be used. The top membrane material is entirely or partially made of antibacterial breathable membrane material for the permeation of sublimated water. Preferably, a mature PE spinning membrane (Tyvek membrane) or expanded polytetrafluoroethylene membrane (ePTFE membrane) on the market can be used according to the compatibility of the material and liquid.

[0031] In this embodiment, in the implementation case where the internal frame 7 is used to form the liquid loading area, the liquid loading area can be formed by the internal frame 7 and the bottom film 62. The frame ensures that the bottom film 62 remains flat during the freeze-drying process, and together with the bottom film 62, forms a container space with an open top for containing the freeze-dried liquid.

[0032] In this embodiment, when the internal frame 7 is used, several reinforcing ribs can be provided on the top of the frame to prevent the top membrane material from contacting the feed liquid during the freeze-drying process and affecting the freeze-drying quality. like Figure 1 to Figure 2 As shown, the flexible container is made of two membrane materials, wherein the bottom membrane material is a freeze-drying membrane made of polypropylene, and the top membrane material is a bacteria-blocking breathable membrane made of expanded polytetrafluoroethylene. A bag mouth is welded to the top membrane material, which is connected to a low-temperature resistant pipeline made of PVC material, and the end of the pipeline is blocked with a plug. A built-in frame 7 is welded on the bottom membrane 62, and the material is low-temperature resistant polypropylene. Several reinforcing ribs are arranged on the top of the built-in frame 7 to prevent the top membrane material from sagging and contacting the liquid during the freeze-drying process. A passive door 5 is also welded on the bottom membrane material, and its material is made of low-temperature resistant polypropylene.

[0033] In this embodiment, the connection process between the built-in frame 7 and the bottom film 62 can be selected from welding, gluing, bonding, mechanical connection, etc. Preferably, polyethylene or polypropylene can be selected according to the welding compatibility with the film material. When the built-in frame 7 is used, several reinforcing ribs can be set on the top of the frame to prevent the top film material from contacting the feed liquid during the freeze-drying process and affecting the freeze-drying quality. An external device can also be used to fix the top film material.

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

[0035] Specifically, the first transmission interface is a transmission interface capable of transmitting liquid into the bag body and maintaining sterility. Preferably, a low-temperature resistant hose 1 that can be aseptically connected and aseptically disconnected and maturely used in the market can be used. The container is connected to the liquid storage container using aseptic connection technology, and after the liquid is injected, it is disconnected from the liquid storage container using aseptic disconnection technology to ensure that the liquid is not contaminated during the liquid injection process. The pipeline has been maturely applied to related consumables in low-temperature freezing, freeze-thaw and other process links. Preferably, the material is made of PVC.

[0036] In this embodiment, preferably, the second transmission interface is arranged on the bottom film 62 of the flexible container; the first transmission interface adopts the passive door 5 in the double door system. Specifically, the double door system is also called the α-β door system, or the AB door system (for example: the DPTE system of Getinge) in the industry. When so called, the passive door 5 is also called the β door or the B door. The double door system is widely used in the cross-level transportation of materials in the fields of medicine, biology, pharmaceuticals, chemicals, nuclear power, etc. It is a verified system that can effectively prevent the exchange between the contents and the environment during the transmission process, and play a role in preventing pollution or protecting users. With years of development, the structure of the passive door 5 in the double door system has become a mature public technology, which at least includes a door plate with a flange, which is used to fit with the active door to open the passive door 5. At least one valve body is included, and the valve body 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 the double-door system in the pharmaceutical industry is mainly in a room temperature environment or an environment that requires high temperature and moist heat sterilization. Therefore, the material for making the passive door 5 mainly considers materials suitable for room temperature or high temperature, such as polycarbonate, stainless steel, etc. The process used in the present invention is freeze-drying, so the material selection of the passive door 5 mainly considers low temperature resistance. For disposable use, preferably, polypropylene can be used, which is a material widely used in low-temperature freezing consumables. As is well known, plastics such as polysulfone and peak can also be used in low-temperature environments, but they are more expensive. In addition, in some scenarios, stainless steel can be used to make the valve body, which is connected to the bag body by mechanical connection. When in use, only the bag body part is disposable, and the stainless steel valve body can be reused.

[0037] In the present invention, the passive door 5 is a window for material transmission, and can be opened by the active door during the liquid injection stage to add liquid into the frame. After the freeze-drying is completed, the passive door 5 can be opened by the active door to aseptically transfer the freeze-dried powder to the powder processing equipment.

[0038] Although the use of the passive door 5 to add liquid is a feasible and proven method, its operation is relatively complicated. Therefore, the aseptic transmission interface of the liquid described in the present invention can be achieved by welding the bag mouth connection pipeline on the bag body. Use mature aseptic connectors on the market, or aseptic pipe connection machines and other technologies to connect to the liquid storage container to achieve liquid filling. After the filling is completed, the aseptic disconnection technology is used to reseal the container. The above-mentioned aseptic connection and aseptic disconnection technologies are mature technologies in the industry, and many manufacturers on the market provide corresponding equipment and consumables. No further details are given in the present invention. When using pipeline injection, a pipeline that can withstand the freeze-drying process must be used. Preferably, a low-temperature resistant pipeline made of PVC material can be used, which has been maturely used in cell freezing, freeze-thawing and other processes.

[0039] The working principle of this embodiment is: The container is produced in a clean environment and sterilized with gamma rays in advance. When using, the user can use it by unpacking the product package. The specific operation 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, the process does not require Class 100 environmental protection, and the freeze dryer does not need to be cleaned or sterilized online. (2) Use a verified pipe connection machine to connect the liquid storage container. Use a peristaltic pump to fill the liquid into the frame inside the container.

[0040] (3) After filling to the required volume, the injection pipeline is disconnected using a sterile disconnector, and the pipeline is resealed. Therefore, Class 100 environmental protection is no longer required during the injection process. (4) Close the door of the freeze dryer and start the freeze drying process. Since the container is a fully 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 completed, take out 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 collecting device, and open the active door.

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

[0044] (8) After the powder is collected, close the active door. Since the powder transmission adopts a mature system that has been verified in the industry, this process does not require the protection of a Class 100 environment. This completes the freeze-drying process. Example

[0045] like Figures 3 to 8 As shown, the second embodiment is further modified on the basis of the first embodiment. The second embodiment includes the technical contents disclosed in the first embodiment, and the technical contents of the second embodiment and the first embodiment are not repeated here. The differences between the second embodiment and the first embodiment are described below.

[0046] This embodiment provides a disposable container suitable for freeze-drying process, which includes: a flexible container; the flexible container is a bag structure with a bacteria barrier function; the flexible container forms a liquid loading area that maintains the geometric shape of the liquid by setting a frame structure. In this embodiment, 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 film 62 of the flexible container, and the two together form a tray-shaped liquid loading area. The flexible container has a first transmission interface for transmitting liquid to the inside and maintaining sterility; the flexible container has a second transmission interface for transmitting powder to the outside and 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. There are many freeze-dried membranes on the market that have been maturely applied, and common materials mainly use polyethylene or polypropylene. Considering that the sublimated water in the freeze-drying process needs to pass through the wall of the flexible container, the flexible container at least contains part of the antibacterial breathable membrane material. The mature membrane materials used on the market include Tyvek membrane made of polyethylene spinning and filter membrane made of expanded polytetrafluoroethylene. With the development of disposable technology for biopharmaceuticals, there are many references on the market for splicing membrane materials into bag bodies. Two pieces of membrane materials can be welded to form a flat bag body, or several pieces of membrane materials can be spliced ​​to form a three-dimensional bag body. Considering the heat transfer requirements of liquids during freeze-drying, the liquid level position is usually not too high, that is, the size requirements of the bag body in the vertical direction are not high. Therefore, preferably, the overall structure of the bag body can adopt a flat bag welded by two pieces of membrane materials. Among them, the bottom is in contact with the freeze-drying panel, and the mature freeze-drying membrane used on the market can be used. The top membrane material is entirely or partially made of antibacterial breathable membrane material for the permeation of sublimated water. Preferably, a mature PE spinning membrane (Tyvek membrane) or expanded polytetrafluoroethylene membrane (ePTFE membrane) on the market can be used according to the compatibility of the material and liquid.

[0048] Preferably, the external frame is a tray-like structure, and magnets 8 are arranged at the four corners of the external frame; a bracket 4 is welded to the inner surface of the bottom membrane 62 of the flexible container, a magnet 8 is arranged in the foot of the bracket 4, and a cross reinforcement rib is arranged on the top of the bracket 4.

[0049] Preferably, when the liquid loading area is composed of an external frame, the external frame can be designed into a tray shape. Magnets 8 are arranged on the tray, preferably, they can be arranged at the four corners of the tray. A bracket 4 is welded on the bottom film 62, and a magnet 8 is arranged in the foot of the bracket 4. When in use, the magnet 8 in the bag body is docked with the magnet 8 on the tray to achieve the purpose of flattening the bottom film 62 and making the heat transfer uniform.

[0050] The external frame can be integrated with the freeze dryer, and the tray-shaped freeze drying panel can be directly used as a support. The integration scheme of the tray and the freeze dryer can refer to the mature flap freeze dryer on the market. When the bag body of the present invention is used in conjunction with the flap freeze dryer, the freeze dryer no longer needs to be designed with online cleaning and online sterilization devices, and the pouring of the powder becomes easier to operate.

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

[0052] The container is produced in a clean environment and sterilized with gamma rays in advance. When using, the user can use it by unpacking the product package. The specific operation 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, the process does not require Class 100 environmental protection, and the freeze dryer does not need to be cleaned or sterilized online.

[0053] (2) Align the magnets 8 at the four corners of the bag with the magnets 8 at the four corners of the tray and flatten the bottom film 62.

[0054] (3) Use a verified pipe connection machine to connect the liquid storage container. Use a peristaltic pump to fill the liquid into the frame inside the container.

[0055] (4) After filling to the required volume, the injection pipeline is disconnected using a sterile disconnector, and the pipeline is resealed. Therefore, Class 100 environmental protection is no longer required during the injection process.

[0056] (5) Close the door of the freeze dryer and start the freeze drying process. Since the container is a fully 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 completed, 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 collecting device, and open the active door.

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

[0060] (9) After the powder is collected, close the active door. Since the powder transmission adopts a mature system that has been verified in the industry, this process does not require the protection of a Class 100 environment. This completes the freeze-drying process.

[0061] In summary, using the product of the present invention, the injection of the freeze-dried liquid adopts aseptic connection and aseptic disconnection technology, the bag body can ensure the penetration of sublimated water under the premise of preventing pollution during the freeze-drying process, and the collection of freeze-dried powder adopts aseptic transmission technology. The protection of the hundred-level environment is no longer required in the entire process. Therefore, the isolator is no longer a necessary equipment during production. Since the container is produced in a clean environment and sterilized by radiation, wet heat or ethylene oxide, the cleaning and sterilization equipment at the freeze-drying production site is no longer a necessary equipment. Therefore, the overall investment of the freeze-drying production line has dropped significantly. At the same time, due to the reduction of necessary equipment, the area of ​​the production workshop and the construction of the workshop public system can also be reduced simultaneously, which will further reduce the initial investment and later operating costs of the production line. In addition, the reduction of equipment also simultaneously reduces the cycle and cost of production line verification, which greatly shortens the production line production cycle. At the same time, the reduction of equipment also speeds up the efficiency of later batch production, because it is no longer necessary to do cleaning and sterilization during batch production, and it is no longer necessary to do isolator performance verification, and the freeze dryer does not need to do online cleaning and online sterilization. In addition, the use of a flip freeze dryer can effectively simplify the process steps of powder discharging.

[0062] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein with equivalents. However, these modifications or replacements 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 process, characterized in that: include: Flexible containers; The flexible container is a bag structure with a bacteria-proof barrier function; The flexible container forms a liquid loading area that maintains the geometric shape of the liquid by providing a frame structure; The flexible container has a first transfer interface for transferring liquid into the interior thereof while maintaining sterility; The flexible container has a second transfer interface for transferring the powder to the exterior thereof while maintaining sterility.

2. The disposable container suitable for freeze-drying process according to claim 1, characterized in that: The flexible container is formed by splicing a plurality of membrane materials; at least one membrane material is a breathable membrane with a bacteria-blocking function.

3. The disposable container suitable for freeze-drying process according to claim 1, characterized in that: 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 film of the flexible container, and the two together form a liquid loading area with an open top.

4. The disposable container suitable for freeze-drying process according to claim 4, characterized in that: A plurality of reinforcing ribs are arranged on the top of the built-in frame.

5. The disposable container suitable for freeze-drying process according to claim 1, characterized in that: 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 film of the flexible container, and the two together form a tray-shaped liquid loading area.

6. The disposable container suitable for freeze-drying process according to claim 7, characterized in that: The external frame is a tray-shaped structure, a bracket is welded on the inner surface of the bottom film of the flexible container, and the external frame and the bracket are connected via a coupling fixing structure.

7. The disposable container suitable for freeze-drying process according to claim 1, characterized in that: The first transmission interface is arranged on the top film of the flexible container; the first transmission interface is a low-temperature resistant hose used for aseptic connection and aseptic disconnection.

8. The disposable container suitable for freeze-drying process according to claim 1, characterized in that: The second transmission interface takes the form of a passive door in a double-door system.

9. A freeze-drying method, characterized in that: A disposable container suitable for freeze-drying process as claimed in any one of claims 1 to 8 is used.

10. The freeze-drying method according to claim 9, characterized in that The steps include: placing the flexible container in a freeze dryer; The freeze-dried liquid is filled into the flexible container through the first transmission interface by using an aseptic connection technique, and after the filling is completed, the first transmission interface is sealed by using an aseptic disconnection technique; Start the freeze dryer to perform freeze drying; After freeze-drying is completed, the flexible container is taken out, and the freeze-dried powder is aseptically transferred to the powder equipment through the second transfer interface.

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