A device for aseptic pharmaceutical liquid preparation and transfer

Abstract

The application provides a device for sterile drug liquid preparation and transfer, a preparation assembly is used for preparation and sterile treatment of sterile drug liquid accessories, and the preparation assembly is arranged in a non-sterile environment; a first ingredient tank is used for preparation of sterile drug liquid main raw materials, the first ingredient tank is arranged in a sterile environment, and the first ingredient tank is connected with the preparation assembly; a second ingredient tank is movably arranged in the non-sterile environment, the second ingredient tank is in a sterile state, and the second ingredient tank is connected with the first ingredient tank; a power source device can generate power, so that the sterile drug liquid accessories are prepared and sterilized, enter the first ingredient tank, and carry the sterile drug liquid main raw materials in the first ingredient tank into the second ingredient tank; and the second ingredient tank can be moved to the vicinity of a filling line and be sterilely connected with the filling line. The device can ensure continuous supply of materials between different clean environments, realize flexible matching in the preparation process of the sterile drug liquid, and keep the sterility of the materials.

Description

Technical Field

[0001] This utility model relates to the field of pharmaceutical technology, and in particular to a device for the preparation and transfer of sterile drug solutions. Background Technology

[0002] In the biopharmaceutical field, pharmaceutical workshops are typically classified into Class A, Class B, Class C, and Class D clean areas, with the cleanliness level ranking as follows: Class A > Class B > Class C > Class D. In the production process of sterile pharmaceutical solutions using non-terminally sterilized processes, sterility must be ensured during the preparation and filling of the sterile solution. This process involves multiple operational steps, each with different cleanliness requirements. For example, solution preparation and filling equipment are generally located in a Class A clean area. The preparation, temporary storage, and transfer of sterile materials and equipment can be carried out in a Class B clean area. The preparation and handling of non-sterile solutions and non-sterile equipment can be carried out in a Class C or Class D clean area.

[0003] The production and application of sterile pharmaceutical solutions require transfer between areas with different cleanliness levels. However, during the transfer process, cross-level transportation of materials between areas with different cleanliness levels can easily lead to contamination of the materials, posing challenges to their quality and safety.

[0004] Therefore, it is important to design a device for the preparation and transfer of sterile drug solutions to ensure the quality and safety of sterile drug solutions during the preparation and transfer process. Utility Model Content

[0005] In view of this, this application provides an apparatus for the preparation and transfer of sterile drug solutions, which can ensure the continuous supply of materials between different clean environments, while achieving flexible matching in the sterile drug solution preparation process, maintaining the sterility of materials, reducing the complexity of operation and the problem of product contamination during the transfer process, and ensuring that the quality of sterile drug solutions is not affected during the transfer process.

[0006] In a first aspect, embodiments of this application provide an apparatus for the preparation and transfer of sterile pharmaceutical solutions, comprising: A preparation component is used for the preparation and aseptic processing of sterile pharmaceutical excipients. The preparation component is located in a first clean environment, which is a non-sterile environment. The first mixing tank is used for the preparation of sterile pharmaceutical liquid main raw materials. The first mixing tank is set in a second clean environment, which is a sterile environment. The first mixing tank is connected to the preparation component. The second ingredient tank is movable within the third clean environment, which is a non-sterile environment. The second ingredient tank is sterile, and it is connected to the first ingredient tank. A power source device is provided, which is capable of generating power so that the sterile pharmaceutical excipients, after being prepared and sterilized, enter the first mixing tank and carry the sterile pharmaceutical main raw material in the first mixing tank into the second mixing tank. The filling line includes a second ingredient tank that can be moved to a location adjacent to the filling line and aseptically connected to it.

[0007] In some embodiments, the main raw material of the sterile pharmaceutical solution includes active pharmaceutical ingredients that cannot be sterilized by filtration.

[0008] In some embodiments, the sterile pharmaceutical excipients include solvents and excipients, and the preparation assembly includes an excipient preparation tank and a solvent connection tube. The excipient preparation tank is used for preparing the excipients, and the solvent is disposed in the solvent connection tube. The excipient preparation tank is connected to the solvent connection tube.

[0009] In some embodiments, the preparation component further includes a sterile filtration device connected to the excipient preparation tank and the solvent connection pipe, respectively, and the sterile filtration device is connected to the first ingredient tank via a pipeline.

[0010] In some embodiments, the number of excipient preparation tanks is at least one; and / or both the excipient preparation tank and the solvent connection pipe are movably disposed within the first clean environment, while the aseptic filtration device is fixedly disposed within the first clean environment.

[0011] In some embodiments, the number of the second ingredient tanks is at least one, and the device further includes a connector for aseptic docking of the second ingredient tanks and the filling line, the connector comprising: A first operating valve is used to connect to the second batching tank, and one end of the first operating valve is connected to a first pipeline. A second operating valve is used to connect to the filling line, and the second operating valve is connected to the first operating valve through the first pipeline; A third operating valve is disposed on one side of the first pipeline, and one end of the third operating valve is connected to a second pipeline. The fourth operating valve is connected to the third operating valve through the second pipeline, and the first pipeline and the second pipeline are in a connected state; The third operating valve is used to introduce sterilizing gas into the connector, and the fourth operating valve is used to discharge the sterilizing gas from the connector.

[0012] In some embodiments, the first and second operating valves are both manual valves, and the third and fourth operating valves are both pneumatic valves; and / or The first operating valve, the second operating valve, the third operating valve, and the fourth operating valve are all diaphragm valves, and the diaphragm material of the diaphragm valve includes at least one of EPDM rubber, polytetrafluoroethylene, fluororubber, and perfluoroethylene propylene.

[0013] In some embodiments, the fourth operating valve includes an inlet end and an outlet end disposed opposite to each other, the outlet end being provided with a temperature sensor; and / or At least one of the first operating valve, the first pipeline, and the second operating valve is equipped with a temperature sensor; and / or A temperature sensor is installed on the outside of the connection point between the first pipeline and the second pipeline.

[0014] In some embodiments, the filling line includes a first filling line that operates within a fourth clean environment, which is a sterile environment. The second ingredient tank can be moved to a location adjacent to the first filling line and aseptically connected to the first filling line.

[0015] In some embodiments, the filling line further includes a second filling line, which is located in a fifth clean environment, the fifth clean environment being non-sterile, and the second filling line being located within a fully enclosed isolation device under sterile conditions. The second ingredient tank can be moved to the vicinity of the second filling line and aseptically connected to the second filling line.

[0016] The device for preparing and transferring sterile drug solutions provided in this application has at least the following advantages: The device of this application can realize the preparation, transfer, and filling of sterile drug solutions across different levels. Specifically, the preparation and transfer of sterile drug solutions are achieved through the arrangement and corresponding connections of a preparation component, a first mixing tank, a second mixing tank, a power source device, and so on. The preparation component is used for the preparation and sterilization of sterile drug solution excipients. The first mixing tank is used for the preparation of the main raw material of the sterile drug solution. The power source device introduces the sterile drug solution excipients in a sterile state into the first mixing tank within a second clean environment, and carries the sterile drug solution main raw material prepared in the first mixing tank into the second mixing tank for temporary storage. The second mixing tank is located in a third clean environment, which is a non-sterile environment. The materials in the second mixing tank are sterile, and the materials have essentially completed the preparation of the sterile drug solution. Furthermore, the second mixing tank of this application is movable and located in the third clean environment. The second mixing tank can be moved to the vicinity of the filling line and sterilely docked with the filling line to complete the filling of the sterile drug solution. This device enables the transfer of raw materials for sterile pharmaceutical solutions across three clean environments: a first, a second, and a third. It maintains the sterility of materials during transfer, reduces product contamination, and ensures the quality of the sterile pharmaceutical solution remains unaffected during transfer. Simultaneously, the second mixing tank is movable, allowing for flexible matching during sterile pharmaceutical solution preparation and making it suitable for complex production environments. Furthermore, this device eliminates the need for high-cost clean environments for both the preparation and transfer of sterile pharmaceutical solutions, significantly reducing investment costs. Other features and advantages of the embodiments of this application will be set forth in the following description, and will be apparent in part from the description, or may be learned by practicing the embodiments of this application. The objects and other advantages of the embodiments of this application are realized and obtained in accordance with the structures particularly pointed out in the description and the drawings. Attached Figure Description

[0017] To more clearly illustrate the technical solutions of the embodiments of this utility model, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of this utility model. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0018] Figure 1 A schematic diagram of a device for preparing and transferring sterile drug solutions, provided as an embodiment of this application; Figure 2 This is a schematic diagram of the structure of the connector provided in the embodiments of this application; Figure 3 A schematic diagram of the structure of another device for preparing and transferring sterile drug solutions provided in the embodiments of this application; Figure 4A schematic diagram of the structure of another device for preparing and transferring sterile drug solutions provided in the embodiments of this application; Figure 5 A schematic diagram of a device for preparing and transferring sterile drug solutions is provided as an embodiment of this application.

[0019] The accompanying drawings, which are incorporated in and form part of this specification, illustrate embodiments consistent with this application and, together with the description, serve to explain the principles of this application.

[0020] In the attached image: 1-Preparation components; 11-Auxiliary material preparation tank; 12- Solvent connecting tube; 13-Sterile filtration device; 2-First batching tank; 3-Second batching tank; 4-Power source device; 5- Filling line; 51-First filling line; 52 - Second filling line; 53 - Fully enclosed isolation device; 6-Connectors; 61 - First operating valve; 62-First pipeline; 63 - Second operating valve; 64 - Third operating valve; 65 - Second pipeline; 66 - Fourth operating valve; 67 - Temperature sensor; 100-First Cleanest Environment; 200 - Second Clean Environment; 300 - Third Clean Environment; 400 - Fourth Clean Environment; 500 - Fifth Clean Environment. Detailed Implementation

[0021] To better understand the technical solution of this application, the embodiments of this application will be described in detail below with reference to the accompanying drawings.

[0022] It should be understood that the described embodiments are merely some, not all, of the embodiments in this application. All other embodiments obtained by those skilled in the art based on the embodiments in this application without inventive effort are within the scope of protection of this application.

[0023] The terminology used in the embodiments of this application is for the purpose of describing particular embodiments only and is not intended to be limiting of this application. The singular forms “a,” “the,” and “the” used in the embodiments of this application and the appended claims are also intended to include the plural forms unless the context clearly indicates otherwise.

[0024] It should be understood that the term "and / or" used in this article is merely a description of the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can represent: A existing alone, A and B existing simultaneously, and B existing alone. Additionally, the character " / " in this article generally indicates that the preceding and following related objects have an "or" relationship.

[0025] It should be noted that the directional terms such as "upper," "lower," "left," and "right" described in the embodiments of this application are used to describe the angles shown in the accompanying drawings and should not be construed as limiting the embodiments of this application. Furthermore, in the context, it should be understood that when it is mentioned that an element is connected "upper" or "lower" to another element, it can be directly connected to the other element "upper" or "lower," or indirectly connected to the other element "upper" or "lower" through an intermediate element.

[0026] To ensure the quality and safety of sterile pharmaceutical solutions during preparation and transfer, Related Technology 1 employs a Class A cleanroom environment for mixing and preparation of the pharmaceutical solution before filling. Specifically, the sterile pharmaceutical solution preparation equipment is located within a Class A cleanroom. Under the protection of the Class A cleanroom, sterilized active ingredients (APIs) and other solutions filtered through sterile filters are mixed, prepared, and stored according to the preparation process. The prepared pharmaceutical solution is then connected to the filling line in the Class A environment to complete the filling of the sterile pharmaceutical product. Related Technology 1 requires both the preparation and transfer of the pharmaceutical solution to be carried out within a Class A cleanroom environment, significantly increasing the overall environmental control and hardware investment costs. This cost becomes particularly high when preparing large quantities.

[0027] Related technology 2 involves preparing the base solution in a low-cleanliness area, followed by aseptic filtration, and finally product filling. Specifically, the drug solution is mixed and prepared using an open feeding method. The prepared solution is non-sterile at this stage. Microorganisms are then removed through multi-stage filtration, and the final filtrate is aseptically stored in a sterile storage container. Finally, the solution in the storage container is connected to the filling line via a rigidly connected tubing, which has already been sterilized, completing the product filling process. Related technology 2 is only suitable for preparing products that can pass sterile filtration. For products that cannot pass sterile filtration, this method has a significant impact on product quality.

[0028] Furthermore, in related technologies 1 and 2, the connection between areas with different cleanliness levels usually requires the installation of AB valves or similar structures to avoid material contamination. However, the sterilization process of AB valves is complex and there are blind spots in cleaning.

[0029] In view of this, this application provides an apparatus for the preparation and transfer of sterile drug solutions. Figure 1 This is a schematic diagram of the structure of the above-mentioned device provided in an embodiment of this application, as shown below. Figure 1 As shown, it includes: Preparation component 1 is used for the preparation and sterile treatment of sterile pharmaceutical excipients. Preparation component 1 is set in the first clean environment 100, which is a non-sterile environment. First mixing tank 2 is used for the preparation of sterile drug solution main raw materials. First mixing tank 2 is set in second clean environment 200. Second clean environment 200 is a sterile environment. First mixing tank 2 is connected to mixing component 1. The second ingredient tank 3 is movably installed within the third clean environment 300, which is a non-sterile environment. The second ingredient tank 3 is in a sterile state and is connected to the first ingredient tank 2. The power source device 4 can generate power so that the sterile drug solution excipients, after being prepared and sterilized, enter the first mixing tank 2 and carry the sterile drug solution main raw materials prepared in the first mixing tank 2 into the second mixing tank 3. The second batching tank 3 can be moved to the vicinity of the filling line 5 and aseptically connected to the filling line 5.

[0030] The device described in this application can realize the preparation, transfer, and filling of sterile drug solutions across different levels. Specifically, the preparation and transfer of sterile drug solutions are achieved through the arrangement and corresponding connections of the preparation component 1, the first mixing tank 2, the second mixing tank 3, and the power source device 4. The preparation component 1 is used for the preparation and sterilization of sterile drug solution excipients. The first mixing tank 2 is used for the preparation of sterile drug solution main raw materials. The power source device 4 introduces the sterile drug solution excipients into the first mixing tank 2 within the second clean environment 200, and carries the sterile drug solution main raw materials prepared in the first mixing tank 2 into the second mixing tank 3 for temporary storage. The second mixing tank 3 is located within the third clean environment 300, which is a non-sterile environment. The materials in the second mixing tank 3 are sterile, and the materials have essentially completed the preparation of sterile drug solutions. Furthermore, the second mixing tank 3 of this application is movable and positioned within the third clean environment 300. The second mixing tank 3 can be moved to the vicinity of the filling line 5 and aseptically connected to the filling line 5 to complete the filling of the sterile drug solution. This device enables the cross-level transfer of raw materials for the sterile drug solution between the first clean environment 100, the second clean environment 200, and the third clean environment 300, maintaining the sterility of the materials during transfer, reducing product contamination during transfer, and ensuring that the quality of the sterile drug solution is not affected during transfer. Simultaneously, the movable second mixing tank 3 allows for flexible matching during the sterile drug solution preparation process, making it suitable for complex production environments. In addition, this device eliminates the need for both the preparation and transfer of the sterile drug solution in high-cost clean environments, significantly reducing investment costs.

[0031] The apparatus for the preparation and transfer of sterile pharmaceutical solutions disclosed in this application ensures a continuous supply of materials between different processes, has a clear material transfer path and operating procedure, and can reduce the risk of material contamination, improve production efficiency, and meet GMP requirements. In this application, the first clean environment 100 can be a Class C clean area environment or a Class D clean area environment, the second clean environment 200 can be a Class A clean area environment or a Class B clean area environment, and the third clean environment 300 can be a Class C clean area environment or a Class D clean area environment. It can be understood that the first clean environment 100 and the third clean environment 300 can be environments of the same cleanliness level, or the first clean environment 100 and the third clean environment 300 can be the same area.

[0032] It is understood that before the device of this application is used, the configuration component 1 and the first ingredient tank 2, as well as the first ingredient tank 2 and the second ingredient tank 3 are connected by pipes, and the pipes have been sterilized.

[0033] In some embodiments, the main raw material for sterile drug solutions refers to the main raw materials required for the preparation of sterile drug solutions, including active pharmaceutical ingredients (APIs) that cannot be sterilized by filtration. That is, the device of this application is mainly used for the preparation of sterile drug solutions containing active pharmaceutical ingredients that cannot be sterilized by filtration. For example, active pharmaceutical ingredients (APIs) that cannot be sterilized by filtration include the following: a. Cell therapy products and cell-derived products, such as cell lysates, semi-purified extracts, etc. b. Certain high-viscosity drug solutions or those containing large particles, which may not be able to pass through a 0.22 μm filter, or may cause filter clogging during the filtration process. c. Certain drug solutions containing proteins or biomolecules, which may adsorb onto the filter surface, leading to reduced filtration efficiency, or even preventing sterilization through filtration.

[0034] In some embodiments, sterile pharmaceutical excipients refer to auxiliary raw materials required for the preparation of sterile pharmaceutical solutions, mainly including excipients and solvents. Excipients may include buffer solutions, stabilizers, and excipients, etc.

[0035] In some implementations, continue as Figure 1 As shown, the preparation component 1 includes an excipient preparation tank 11, a solvent connection tube 12, and an aseptic processing device 13. The solvent connection tube 12 is connected to the excipient preparation tank 11, and the aseptic processing device 13 is connected to both the excipient preparation tank 11 and the solvent connection tube 12. The excipient preparation tank 11 is used for preparing excipients, such as buffer solutions. The solvent connection tube 12 is used to provide the solvent, which can be used as a solvent for the excipients or as a solvent for the entire aseptic solution. It can be understood that the solvent connection tube 12 connects to the container providing the solvent. Figure 1 Not shown in the image.

[0036] In some embodiments, the preparation of excipients only needs to be completed in a lower-level clean area. The excipient preparation tank 11 used in this application can be located in the first clean environment 100, that is, the excipient preparation tank 11 is located in a Class C or Class D clean area to meet the cleanliness requirements of the excipients. Correspondingly, the solvent connection pipe 12 is also located in a Class C or Class D clean area. The aseptic filtration device 13 is used to aseptically filter the already prepared aseptic drug solution excipients in the excipient preparation tank 11 and the solvent in the solvent connection pipe 12. The aseptic treatment device 13 is connected to the first preparation tank 2, and after the aseptic drug solution excipients are prepared and aseptically treated, they are introduced into the first preparation tank 2 within the second clean environment 200.

[0037] In some embodiments, the number of excipient preparation tanks 11 is at least one. The number of excipient preparation tanks 11 can be set according to the required amount of excipients for the sterile drug solution. The number of excipient preparation tanks 11 can be one, two, three, or four, etc. This allows for more flexible addition of excipients and avoids cross-contamination caused by using a single excipient preparation tank 11.

[0038] In some embodiments, the excipient preparation tank 11 and solvent connection pipe 12 are movably disposed within the first clean environment 100. The movable excipient preparation tank 11 allows for flexible adjustment of the production process, improving production flexibility, and also facilitates maintenance and cleaning. The aseptic filter device 13 is fixed within the first clean environment 100. When the excipient preparation tank 11 and solvent connection pipe 12 need to be connected to the aseptic filter device 13, a temporary connection can be achieved through flexible hoses or the like.

[0039] In some embodiments, the auxiliary material preparation tank 11 may be equipped with a mechanism such as casters or rails to enable movement, thereby improving the flexibility of the auxiliary material preparation tank 11. The solvent connecting pipe 12 is fixedly connected to the auxiliary material preparation tank 11. Preferably, the movable mechanism on the auxiliary material preparation tank 11 may also have a braking function. In some embodiments, the aseptic filtration device 13 includes a pipe and at least one aseptic filter installed on the pipe. The number of aseptic filters can be one, two, three, or four, etc., depending on the requirements of aseptic processing, and this application does not limit this. The aseptic filter can remove bacteria, viruses, and other microorganisms from the aseptic pharmaceutical excipients, making them sterile before they enter the first mixing tank 2.

[0040] In some implementations, the sterile filter has a membrane pore size of 0.22 μm, which can efficiently remove bacteria and fungi and ensure the sterility of materials.

[0041] In some embodiments, the first mixing tank 2 is located within the second clean environment 200, i.e., within a Class A clean area environment, thus meeting the environmental requirements for the main raw material of the sterile pharmaceutical solution. This application may use a Class B clean area environment as the background area for a Class A clean area environment.

[0042] In some embodiments, the main raw material of the sterile pharmaceutical solution of this application is a sterile pharmaceutical active ingredient. It is understood that the pharmaceutical active ingredient can be pre-sterilized by methods such as dry heat sterilization or moist heat sterilization before being added to the first mixing tank 2. Dry heat sterilization generally involves introducing high-temperature dry air into the pharmaceutical active ingredient, causing oxidation, denaturation, and electrolyte concentration in the proteins and enzymes, thus achieving sterilization. Common dry heat sterilization methods include oven sterilization and flame sterilization. Moist heat sterilization generally involves introducing high-temperature steam into the pharmaceutical active ingredient. When the high-temperature steam condenses on the surface of the pharmaceutical active ingredient, it releases a large amount of latent heat, raising the surface and internal temperature of the pharmaceutical active ingredient, thereby destroying the proteins and nucleic acids of microorganisms and achieving sterilization. Common moist heat sterilization methods include autoclaving and boiling sterilization.

[0043] In some embodiments, the apparatus of this application further includes sterilization equipment disposed within a first clean environment 100 (sterilization equipment in...). Figure 1 (Not shown in the diagram) The sterilization equipment is connected to the first mixing tank 2 via a pipeline. In the specific implementation process, the active pharmaceutical ingredient is put into the sterilization equipment for sterilization treatment, and after obtaining sterile active pharmaceutical ingredient, it is put into the first mixing tank 2.

[0044] In some embodiments, the second ingredient tank 3 of this application is in a sterile state, that is, the second ingredient tank 3 is sterilized before use.

[0045] In some embodiments, the number of second mixing tanks 3 is at least one, specifically one, two, three, or four, etc., and this application does not impose any limitation. When the excipients and / or main raw materials of the sterile drug solution can be used to prepare different sterile drug solutions, or to prepare sterile drug solutions of different specifications, the number of second mixing tanks 3 can be two or more. In this way, the preparation and transfer route of the sterile drug solution can be optimized, and production efficiency can be improved.

[0046] In some embodiments, the second ingredient tank 3 is movably positioned within the third clean environment 300. Casters, tracks, or other movable structures can be installed on the second ingredient tank 3 to enable its movement. Preferably, the movable mechanism on the second ingredient tank 3 can also have a braking function. Both the auxiliary material preparation tank 11 and the second ingredient tank 3 in this application are movable, allowing for rapid movement from one area to another, reducing waiting time during the production process, improving flexibility, and ensuring the continuity of the production flow. For example, when the second ingredient tank 3 is movable, it indicates that the pipe connected to the second ingredient tank 3 is a flexible hose or similar device that can be moved to a movable position for temporary connection, such as a pneumatic hose or a metal hose. In some embodiments, the pipe connecting the second ingredient tank 3 and the first ingredient tank 2 is a pneumatic hose.

[0047] In some embodiments, after the materials in the excipient preparation tank 11, solvent connection pipe 12, and first mixing tank 2 are collected into the second mixing tank 3, the method further includes: performing a weighing operation on the materials in the second mixing tank 3 to obtain a sterile drug solution. This weighing operation ensures the accurate concentration of the sterile drug solution.

[0048] In some embodiments, the power source device 4 is a device capable of providing power, which repeatedly flushes the excipients in the excipient preparation tank 11 by providing compressed air or pump power, so that the excipients in the excipient preparation tank 11 can enter the first ingredient tank 2 after passing through the aseptic treatment device 13, and so that all the material in the first ingredient tank 2 is replaced in the second ingredient tank 3. This arrangement can obtain a sterile drug solution with sterility, avoiding the need for connecting valves between the excipient preparation tank 11, the first ingredient tank 2, and the second ingredient tank 3. It is understood that before use, the aseptic treatment device 13 and the first ingredient tank 2, as well as the first ingredient tank 2 and the second ingredient tank 3, are connected by pipelines, and the pipelines have already undergone aseptic treatment.

[0049] In some embodiments, the power source device 4 may include an air compressor, a booster pump, and a hydraulic pump, etc. Those skilled in the art can select a suitable power source device according to actual needs, and this application does not impose any restrictions.

[0050] In related technologies, containers storing pre-prepared sterile drug solutions are typically connected to the filling line via AB valves. AB valves, also known as αβ valves, are split-type butterfly valves consisting of an active valve and a passive valve. AB valves prevent microorganisms and other contaminants from entering the connection between the container and the filling line, ensuring the sterility and safety of materials during transfer. However, existing AB valves have the following drawbacks and limitations: First, the AB valve has a complex structure, consisting of an active valve and a passive valve. Before use, the active and passive valves need to be connected, and after connection, a locking mechanism is required to tightly connect the two parts to ensure a seal. Due to the special structure of the AB valve, cleaning and sterilization are not thorough. Specifically, during cleaning and sterilization, the contact surfaces of the active and passive valves, the internal channels, internal dead corners, and external surfaces of the AB valve need to be cleaned and sterilized. The internal dead corners of the AB valve include the connection between the active and passive valves, which usually has millimeter-level gaps. The temperature at these gaps is generally low, causing condensation when sterilizing gases pass through, forming a large condensation area. This not only affects the sterilization effect but may also lead to the growth of unsanitary substances and increase the risk of cross-contamination. In the pharmaceutical field, it is currently impossible to monitor the temperature distribution at various points on the contact surface of the valve plates of the active and passive valves during the sterilization process of AB valves, making it impossible to effectively solve the problem of unsanitary dead corners. Existing improvement methods usually involve designing the valve plate of the AB valve with an eccentric structure to reduce flow resistance. Such a design leads to an increase in the area to be cleaned and sterilized, and a corresponding decrease in the flow rate of cleaning and sterilization, even below the 1.5 m / s flushing flow rate recommended by ASME BPE (American Society of Mechanical Engineers Biopharmaceutical Equipment Standard). This results in insufficient contact between the cleaning agent and the AB valve, leading to inadequate cleaning.

[0051] Secondly, AB valves are configured in the production line to achieve aseptic connection. Each time an AB valve is used, it needs to be reinstalled. Moreover, there are usually multiple passive valves, each corresponding to different types of materials, making the installation process complex. Furthermore, each time an AB valve is installed, the interface and slits of the AB valve need to be sterilized and tested for sealing. Sterilization requires complex verification experiments, and the sterilization effect can only be confirmed by a temperature sensor on the condensate line connected to the AB valve, rather than directly measuring the sterilization effect inside the AB valve, greatly increasing the operational complexity of AB valves.

[0052] Third, there are many quality control points for AB valves (including the quality of AB valve materials, the quality of AB valve welding, the quality of AB valve assembly, and the confirmation of AB valve sterility, etc.). The confirmation of sterility is only one of the steps, which makes the process flow of AB valves more complicated and inconvenient to operate during production line operation.

[0053] Therefore, embodiments of this application provide an apparatus for the preparation and transfer of sterile drug solutions, wherein a connector 6 is provided within the apparatus. Used to achieve aseptic connection between the second batching tank 3 and the filling line 5. Figure 2 This is a schematic diagram of the structure of the connector 6 provided in the embodiments of this application, as shown below. Figure 2 As shown, connector 6 includes: The first operating valve 61 is used to connect to the second batching tank 3, and one end of the first operating valve 61 is connected to the first pipeline 62. The second operating valve 63 is used to connect to the filling line 5. The second operating valve 63 is connected to the first operating valve 61 through the first pipeline 62. The third operating valve 64 is located on one side of the first pipeline 62, and one end of the third operating valve 64 is connected to the second pipeline 65. The fourth operating valve 66 is connected to the third operating valve 64 through the second pipeline 65, and the first pipeline 62 and the second pipeline 65 are in a connected state. The third operating valve 64 is used to introduce sterilizing gas into the connector 6, and the fourth operating valve 66 is used to discharge sterilizing gas from the connector 6.

[0054] The connector 6 of this application is used to achieve aseptic connection between the second mixing tank 3 and the filling line 5. The first operating valve 61, the first pipeline 62, and the second operating valve 63 are used to connect the second mixing tank 3 and the filling line 5. The asepticity of the connector 6 is achieved through the third operating valve 64 and the fourth operating valve 66. Specifically, the connector 6 is connected to both the second mixing tank 3 and the filling line 5. Specifically, the first operating valve 61 is connected to the second mixing tank 3, and the second operating valve 63 is connected to the filling line 5. The first and second operating valves 61 and 63 are closed, while the third and fourth operating valves 64 and 66 are opened. Sterilizing gas enters the connector 6 through the third operating valve 64 and sterilizes it. The sterilized gas is then discharged through the fourth operating valve 66 (the direction of the sterilizing gas's inlet and outlet is...). Figure 2 (Direction indicated by the arrow). It can be understood that, in this application, when the third operating valve 64, the fourth operating valve 66, the first operating valve 61, and the second operating valve 63 are closed, the interior of the connector 6 is in a sealed state.

[0055] Compared to AB valves, the connector 6 in this application has a simple structure, without complex mechanical parts. It is formed by combining valves, eliminating any discontinuity in the mechanical structure. During cleaning and sterilization of the connector 6, the sterilizing gas sequentially enters the second pipeline 65 and the first pipeline 62 through the third operating valve 64, and finally exits from the fourth operating valve 66. The connector 6 has good sealing performance, no structural dead corners, and reduces the risk of microbial growth. During the sterilization process, the sterilizing gas can ensure that the fluid dynamics meet the cleaning requirements and that the sterilization requirements are met through an effective heat transfer path, resulting in high sterilization stability.

[0056] In some embodiments, the sterilizing gas may be, for example, water vapor. Specifically, water vapor can be connected to the connector 6 from the third operating valve 64 and finally discharged from the fourth operating valve 66, which can control the residual amount of cleaning and sterilization to below 0.1%.

[0057] In some embodiments, the first operating valve 61 and the second operating valve 63 are both manual valves, operated by a manual operating device, which is simple, convenient, and highly reliable. The third operating valve 64 and the fourth operating valve 66 are both pneumatic valves, which use a pneumatic power source to drive the valve opening and closing, and have the characteristics of fast response and stable reliability.

[0058] In some embodiments, the first operating valve 61, the second operating valve 63, the third operating valve 64, and the fourth operating valve 66 are all diaphragm valves. Diaphragm valves can control the flow of fluid through the elastic deformation of the diaphragm and have good sealing performance during use.

[0059] In some implementations, the diaphragm valve is made of a flexible, seamless material, such as ethylene propylene diene monomer (EPDM), polytetrafluoroethylene (PTFE), fluororubber (FKM), and perfluoroethylene propylene (FEP).

[0060] In some embodiments, the first operating valve 61, the second operating valve 63, the third operating valve 64, and the fourth operating valve 66 are all inclined to ensure the smooth discharge of liquid during the sterile cleaning process.

[0061] In some embodiments, the first operating valve 61, the second operating valve 63, the third operating valve 64, and the fourth operating valve 66 are all made of stainless steel, for example, 316L.

[0062] In some embodiments, the first operating valve 61 can be directly connected to the second batching tank 3 or connected through a corresponding pipeline, and the second operating valve 63 can be directly connected to the filling line 5 or connected through a corresponding pipeline.

[0063] In some embodiments, the fourth operating valve 66 includes an inlet end and an outlet end disposed opposite to each other, and a temperature sensor 67 is provided at the outlet end of the fourth operating valve 66 to confirm the sterility of the connector 6.

[0064] In some embodiments, at least one of the first operating valve 61, the first pipeline 62, and the second operating valve 63 is provided with a temperature sensor 67 to confirm the sterility of the connector 6.

[0065] In some embodiments, a temperature sensor 67 is provided on the outside of the junction of the first conduit 62 and the second conduit 65 to confirm the sterility of the connector 6.

[0066] Compared to AB valves, which can only place temperature sensors at the end, this application can place temperature sensors 67 on the internal pipeline and valve of the connector 6, as well as on the outside and end of the connector 6, so that temperature can be detected from multiple directions and angles to confirm the sterility of the connector 6.

[0067] Experimental testing showed that the effective cleaning coverage of connector 6 in this application can reach 99.9%. During online sterilization, it can ensure a lethal dose (F0) of more than 8 minutes, achieving a sterility guarantee level. Connector 6 eliminates structural dead zones through a combination of valves (a combination of pneumatic and manual valves), ensuring that fluid dynamics meet cleaning requirements and that sterilization requirements are met through an effective heat transfer path. Under a pure steam pressure of 1.2 bar or higher, the temperature is controlled at 122°C, and the sterilization time is maintained at 30 minutes. The overall sterilization strategy is relatively conventional, with high sterilization stability, further improving the sterility requirements of connector 6 during use.

[0068] In some implementations, continue as Figure 1 As shown, the filling line 5 includes a first filling line 51, which is located within a fourth clean environment 400. The fourth clean environment 400 is a sterile environment, such as a Class A or Class B clean area. The second mixing tank 3 can be moved to a position adjacent to the first filling line 51 for aseptic connection. Specifically, when it is necessary to fill the sterile medication in the second mixing tank 3, the second mixing tank 3 is moved within the fourth clean environment 400 and moved to a position adjacent to the first filling line 51. This increases the flexibility of the production line. Furthermore, the second mixing tank 3 and the first filling line 51 are aseptically connected via a connector 6.

[0069] In some implementations... Figure 3 This is a schematic diagram of the structure of another device provided in the embodiments of this application, as shown below. Figure 3 As shown, the filling line 5 includes a second filling line 52, which is disposed within a fully enclosed isolation device 53 in a sterile environment. The second ingredient tank 3 can be moved to a position adjacent to the fully enclosed isolation device 53 and aseptically connected to the second filling line 52. The fully enclosed isolation device 53 of this application is sterile, thus allowing the second filling line 52 to be placed in a fifth clean environment 500, which is non-sterile, such as a Class C or Class D clean area. This significantly reduces the difficulty of environmental control and lowers costs. The movable nature of the second ingredient tank 3 increases the flexibility of the production line, and the second ingredient tank 3 and the second filling line 52 can be aseptically connected via a connector 6.

[0070] In some implementations, the fully enclosed isolation device 53 may be, for example, a blow-fill-seal machine (BFS device).

[0071] In some implementations... Figure 4 A schematic diagram of another device provided in the embodiments of this application is shown below. Figure 4 As shown, the filling line 5 includes a first filling line 51 and a second filling line 52.

[0072] In some implementations, continue as Figure 4 As shown, when the number of second mixing tanks 3 in this application is set to one, the second mixing tank 3 can be connected to the first filling line 51, or the second mixing tank 3 can be connected to the second filling line 52. When it is necessary to fill the same sterile drug solution of different specifications, the second mixing tank 3 can also be connected to the first filling line 51 and the second filling line 52 respectively. Figure 5 A schematic diagram of another device provided in this application embodiment is shown below. Figure 5 As shown, when the number of second mixing tanks 3 in this application is set to two, the first mixing tank 2 can be connected to the two second mixing tanks 3 respectively. One of the second mixing tanks 3 is connected to the first filling line 51, and the other second mixing tank 3 is connected to the second filling line 52, so as to realize the filling of the same sterile drug solution of different specifications.

[0073] In summary, the apparatus for the preparation and transfer of sterile pharmaceutical solutions in this application achieves one-step mixing operations in areas with different cleanliness levels by incorporating a power source, reducing environmental control difficulties, minimizing personnel involvement, and confirming product sterility. Furthermore, the integration of a movable second mixing tank 3 and connector 6 enables the filling and aseptic connection of sterile pharmaceutical solutions, making it suitable for production environments with numerous products and complex sites, thus reducing production line investment. Compared to existing technologies that use AB valves to connect areas with different cleanliness levels, this application avoids the problems of high cost, complex sterilization processes, and reduced sterilization efficiency associated with using multiple AB valves.

[0074] The above description is only a preferred embodiment of the present utility model and is not intended to limit the present utility model. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present utility model should be included within the scope of protection of the present utility model.

Claims

1. An apparatus for the preparation and transfer of sterile pharmaceutical solutions, characterized in that, include: A preparation component is used for the preparation and aseptic processing of sterile pharmaceutical excipients. The preparation component is located in a first clean environment, which is a non-sterile environment. The first mixing tank is used for the preparation of sterile pharmaceutical liquid main raw materials. The first mixing tank is set in a second clean environment, which is a sterile environment. The first mixing tank is connected to the preparation component. The second ingredient tank is movable within the third clean environment, which is a non-sterile environment. The second ingredient tank is sterile, and it is connected to the first ingredient tank. A power source device is provided, which is capable of generating power so that the sterile pharmaceutical excipients, after being prepared and sterilized, enter the first mixing tank and carry the sterile pharmaceutical main raw material in the first mixing tank into the second mixing tank. The filling line includes a second ingredient tank that can be moved to a location adjacent to the filling line and aseptically connected to it.

2. The apparatus according to claim 1, characterized in that, The main raw materials of the sterile drug solution include active drug components that cannot be sterilized by filtration.

3. The apparatus according to claim 1, characterized in that, The sterile pharmaceutical excipients include solvents and excipients. The preparation assembly includes an excipient preparation tank and a solvent connection tube. The excipient preparation tank is used for preparing the excipients. The solvent is disposed in the solvent connection tube. The excipient preparation tank is connected to the solvent connection tube.

4. The apparatus according to claim 3, characterized in that, The preparation assembly also includes a sterile filtration device, which is connected to the excipient preparation tank and the solvent connection pipe respectively, and the sterile filtration device is connected to the first ingredient tank through a pipeline.

5. The apparatus according to claim 4, characterized in that, The number of the excipient preparation tank is at least one; and / or both the excipient preparation tank and the solvent connection pipe are movably disposed within the first clean environment, and the aseptic filtration device is fixedly disposed within the first clean environment.

6. The apparatus according to any one of claims 1 to 5, characterized in that, The number of the second ingredient tanks is at least one, and the device further includes a connector for aseptic connection between the second ingredient tanks and the filling line, the connector comprising: A first operating valve is used to connect to the second batching tank, and one end of the first operating valve is connected to a first pipeline. A second operating valve is used to connect to the filling line, and the second operating valve is connected to the first operating valve through the first pipeline; A third operating valve is disposed on one side of the first pipeline, and one end of the third operating valve is connected to a second pipeline. The fourth operating valve is connected to the third operating valve through the second pipeline, and the first pipeline and the second pipeline are in a connected state; The third operating valve is used to introduce sterilizing gas into the connector, and the fourth operating valve is used to discharge the sterilizing gas from the connector.

7. The apparatus according to claim 6, characterized in that, The first and second operating valves are both manual valves, while the third and fourth operating valves are both pneumatic valves; and / or The first operating valve, the second operating valve, the third operating valve, and the fourth operating valve are all diaphragm valves, and the diaphragm material of the diaphragm valve includes at least one of EPDM rubber, polytetrafluoroethylene, fluororubber, and perfluoroethylene propylene.

8. The apparatus according to claim 6, characterized in that, The fourth operating valve includes an inlet end and an outlet end disposed opposite to each other, and the outlet end is provided with a temperature sensor; and / or At least one of the first operating valve, the first pipeline, and the second operating valve is equipped with a temperature sensor; and / or A temperature sensor is installed on the outside of the connection point between the first pipeline and the second pipeline.

9. The apparatus according to any one of claims 1 to 5, characterized in that, The filling line includes a first filling line, which is located in a fourth clean environment, which is a sterile environment. The second ingredient tank can be moved to a location adjacent to the first filling line and aseptically connected to the first filling line.

10. The apparatus according to claim 9, characterized in that, The filling line also includes a second filling line, which is set in a fifth clean environment. The fifth clean environment is a non-sterile state, and the second filling line is in a fully enclosed isolation device in a sterile state. The second ingredient tank can be moved to the vicinity of the second filling line and aseptically connected to the second filling line.

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