Bioprocess system

Abstract

To provide a bioprocess system.SOLUTION: A bioprocess system 1 comprises a flow path comprising: a plurality of inlets 7; at least one bio-processing device inlet connection 9a and at least one bioprocessing device outlet connection 9b; a plurality of outlets; and flow path parts of at least some active components 5a, 5b, 5c disposed in the bioprocess system. The bioprocess system also comprises active parts of the active components. The flow path of the bioprocess system is positioned centrally within the bioprocess system and in a vertical orientation, so that the active parts are positioned around the flow path being accessible from outside the bioprocess system and each in connection with a corresponding flow path part of the active component.SELECTED DRAWING: Figure 1a

Description

[Technical Field]

[0001] The present invention relates to a bioprocessing system. [Background technology]

[0002] A bioprocessing system typically comprises several inlets, outlets, pumps, valves, sensors, and flow connections to connected bioprocessing devices, e.g., separation units, e.g., chromatography columns or filtration units. The fluid connection pipes within the system are typically welded to the different components. The systems are often large and must be located in clean rooms. Furthermore, they must be sanitized and serviceable. The connecting pipes and the welds between the pipes and the components can reduce sanitary effectiveness and increase hold-up volume within the system. Summary of the Invention [Problem to be solved by the invention]

[0003] It is an object of the present invention to provide an improved bioprocessing system.

[0004] It is a further object of the present invention to provide an effective bioprocessing system with a small footprint. [Means for solving the problem]

[0005] This is solved for example by a bioprocess system according to claim 1.

[0006] According to one aspect of the present invention, there is provided a bioprocessing system comprising a flow path comprising a plurality of inlets, at least one bioprocessing device inlet connection and at least one bioprocessing device outlet connection, a plurality of outlets, and flow path portions of at least some active components comprised within the bioprocessing system, and active portions of the active components, wherein the flow path of the bioprocessing system is positioned centrally within the bioprocessing system in a vertical orientation, whereby the active portions are positioned around the flow path that is accessible from outside the bioprocessing system, and each connects to a corresponding flow path portion of the active component.

[0007] By locating the flow path vertically and centrally within the bioprocessing system, not only can the footprint of the system be kept small, but air purging within the system is also improved. Furthermore, by locating the flow path centrally and locating the active parts of the active components around the flow path, the active parts are easily accessible from outside the bioprocessing system, which facilitates servicing.

[0008] In one embodiment of the invention, the flow path is created in several sections or in one section by a 3D printer.

[0009] In one embodiment of the present invention, the flow path is at least somewhat self-supporting.

[0010] In one embodiment of the present invention, the flow path is produced by a 3D printer with a thickness adapted to provide the flow path with at least some degree of self-support, which may be different for different portions of the flow path, and / or the flow path is produced by a 3D printer together with additional external support structures.

[0011] In one embodiment of the invention, the active components comprise a number of valves and possibly also one or more pumps and one or more sensing components.

[0012] In one embodiment of the invention, the flow path is fabricated from a corrosion-resistant metal using a 3D printer.

[0013] In one embodiment of the present invention, the bioprocessing system further comprises a support structure, either a central spine located inside the flow path or a frame partially surrounding the flow path, that includes a user interface and tubing connections. [Brief explanation of the drawings]

[0014] [Figure 1a] FIG. 1 illustrates a first side view of a bioprocessing system according to one embodiment of the present invention. [Figure 1b] FIG. 1B is a view of the same bioprocessing system as shown in FIG. 1A from a second side opposite the first side. [Figure 1c] FIG. 1b is a perspective view of the first side of the same bioprocessing system as shown in FIG. 1a. [Figure 1d] FIG. 1b is a perspective view of the second side of the same bioprocessing system shown in FIG. 1a. [Figure 2a] FIG. 1 is a different perspective view of a first side of a bioprocessing system according to one embodiment of the present invention. [Figure 2b] FIG. 1 is a different perspective view of a first side of a bioprocessing system according to one embodiment of the present invention. [Figure 2c] FIG. 2C is a different perspective view of a second side, opposite the first side, of the same bioprocessing system shown in FIGS. 2a and 2b. [Figure 2d] FIG. 2C is a different perspective view of a second side, opposite the first side, of the same bioprocessing system shown in FIGS. 2a and 2b. [Figure 3a]1A-1D are different perspective views of a bioprocessing system according to one embodiment of the present invention. [Figure 3b] 1A-1D are different perspective views of a bioprocessing system according to one embodiment of the present invention. [Figure 4a] FIG. 1b is a perspective view showing two separate portions of the fluid path of a bioprocessing system such as that shown in FIG. 1a. [Figure 4b] FIG. 1c is a perspective view showing two separate portions of the fluid path of a bioprocessing system as shown in FIG. 1b. [Figure 4c] FIG. 1c is a perspective view showing two separate portions of the fluid path of a bioprocessing system as shown in FIG. 1c. [Figure 4d] FIG. 1D is a perspective view showing two separate portions of the fluid path of a bioprocessing system as shown in FIG. 1d. [Figure 5] FIG. 1 is a perspective view of a bioprocessing system according to another embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0015] A bioprocessing system 1 according to one embodiment of the present invention is shown in FIGS. 1a-1d. FIG. 1a is a view from a first side, FIG. 1b is a view from a second side opposite the first side, and FIGS. 1c and 1d are perspective views. The bioprocessing system 1 includes a flow path 3 and several active components 5a, 5b, 5c, 5d, and 5e. The active components include several valves 5a, 5c, and 5d, and optionally at least one pump 5a and several sensing components 5e. The active components include flow path portions 5a', 5b', 5c', 5d', and 5e', respectively, and active portions 5a'', 5b'', 5c'', 5d'', and 5e''. The active portions may be a driving portion 5a'' of a pump, an actuating portion 5b'', 5c'', or 5d'' of a valve, or a sensing portion 5e'' of a sensor. The bioprocessing system 1 may also include other components, as described below.

[0016] Flow path 3 comprises multiple inlets 7, at least one bioprocessing device inlet connection 9a, at least one bioprocessing device outlet connection 9b, and multiple outlets 11. Flow path 3 further comprises flow path portions 5a', 5b', 5c', 5d', 5e' of active components 5a, 5b, 5c, 5d, 5e.

[0017] In this embodiment of the invention, one inlet valve 5b is provided for each inlet 7 and one outlet valve 5d is provided for each outlet 11. Additionally, a bioprocessing device valve 5c is provided at each bioprocessing device inlet and outlet connection 9a, 9b.

[0018] Other components provided in the bioprocessing system 1 according to this embodiment are a filter 21 and a bubble trap 23. A valve 25 is also provided to control the filter 21 and the bubble trap 23. However, these components and valves are not required in all embodiments. Furthermore, although several flow meters 26 and sensors 27 are provided in this embodiment, this may not be necessary and / or may be located at different locations within the system. Bioprocessing devices, e.g., separation or fluid treatment devices, such as chromatography columns, filters, or viral inactivation chambers (reactors), may be connected to the bioprocessing device inlet and outlet connections 9a, 9b and may be part of the bioprocessing system 1 according to the present invention or may be separate parts.

[0019] According to the present invention, the flow path 3 of the bioprocessing system 1 is positioned substantially centrally within the bioprocessing system 1 and in a substantially vertical orientation. Furthermore, the active portions 5a'', 5b'', 5c'', 5d'', 5e'' are positioned substantially around the flow path 3 that are accessible from the outside of the bioprocessing system, and each connects to a corresponding flow path portion 5a', 5b', 5c', 5d', 5e' of the active components 5a, 5b, 5c, 5d, 5e. Due to the central and vertical positioning of the flow path 3, the active components 5a, 5b, 5c, 5d, 5e can be easily accessed from the outside of the bioprocessing system 1 for servicing. Furthermore, the inlet 7 of the flow path 3 is provided at the bottom of the bioprocessing system 1, and the outlet 11 is provided at the top of the bioprocessing system. Thereby, and due to the vertical orientation of the flow path 3, an upward flow can be maintained within the bioprocessing system 1, which improves purging of air from the system.

[0020] According to the present invention, the flow path 3 is at least partially produced by a 3D printer. The entire flow path 3 can be produced in one piece by a 3D printer, or it can be produced in several sections. The material for producing the flow path 3 by a 3D printer can be a corrosion-resistant metal, such as stainless steel, or a polymer with high chemical resistance, such as polypropylene or PEEK. Thanks to the ability to produce the flow path 3 by a 3D printer, the flow path can be made significantly more compact than prior art systems. Welding and TC connections between different components are avoided, thereby saving space and improving hygiene. Furthermore, the connecting tubes can be produced by the printer with any degree of curvature that allows components to be placed close to each other. Furthermore, components produced by a 3D printer can be smaller and more compact than those produced by other production methods. This allows the flow path 3 produced by a 3D printer according to the present invention to be significantly more compact than flow paths in any prior art system. Components can be placed closer together, allowing for a higher density of components within the bioprocessing system. Furthermore, by locating the flow path 3 centrally and vertically within the bioprocessing system 1, the footprint can be kept small.

[0021] For example, in various embodiments, the flow path 3 of the bioprocessing system effectively replaces many conventional parts (such as connectors, clamps, seals, screws, welds, etc.) using fewer individual components fabricated by a 3D printer. Fabricating parts by a 3D printer is thus useful in allowing a reduced number of connectors to be used, and also provides the additional benefit of providing a compact system that is easier to assemble and maintain and reduces the likelihood of inadvertently introducing contaminants into the bioprocessing system during assembly. Thus, the replacement ratio of conventional parts relative to the number of connectors required to provide the flow path 3 is low. For example, in various embodiments, 10 parts can effectively be combined into one, requiring only two connectors in the bioprocessing system. Thus, embodiments of the present invention may result in part replacement ratios of >2:1, >3:1, >5:1, >10:1, etc.

[0022] As a result of the inventive design of bioprocessing system 1, the bioprocessing system has a smaller, lower hold-up volume compared to prior art systems, which is a significant advantage for increasing processing efficiency in the biopharmaceutical industry. The smaller the hold-up volume, the less buffer and solution consumption and volume required for processing. Typically, a bioprocess involves many process cycles, each cycle applying a series of different fluids to a separation or fluid processing device to achieve the objective of a processing step. These fluids are provided through different inlets of the bioprocessing system; alternatively, the fluids and / or fluid properties may already have been changed in upstream processing steps and / or systems connected to one or more inlets of bioprocessing system 1. These fluid switches mean that there is waste of fluid and fluid volume, as the efficiency of switching is directly related to the hold-up volume of the bioprocessing system and components. In the bioprocessing system according to the present invention, the hold-up volume is dramatically reduced, thereby improving separation quality and processing efficiency and reducing processing costs. Separation quality is improved by a smaller hold-up volume, as a large hold-up volume generally negatively impacts the separation resolution obtainable in a chromatography setup. Therefore, reducing hold-up volume and increasing separation quality increases chromatographic purity and yield. Increased purity and yield, in turn, leads to increased efficiency of processes, equipment, and manufacturing facilities and operations. Reducing hold-up volume also reduces the time required to process and pump fluids, which in turn reduces the volume of liquid handled, thereby increasing processing efficiency. Thus, the system according to the present invention provides increased separation and processing quality and / or increased processing efficiency, which ultimately reduces the cost of drug substances and drug treatments provided to patients.

[0023] For example, various conventional bioprocessing systems are known having capacities ranging from 5 L to 1000 L, which have footprints ranging from 20 cm x 21 cm to 1.6 m x 1.5 m. However, various embodiments of the present invention may be used that allow the footprint of the bioprocessing system to be reduced, for example, by at least 30% (e.g., 50%, or even 70% or more). Thus, in embodiments of the present invention, a footprint of approximately 17 cm x 17 cm (approximately 0.03 m) may be used for bioprocessing systems having capacities between 5 L and 1000 L. 2 ) to 1.3m x 1.3m (approx. 1.7m 2 ) footprint (30% reduction), approximately 14cm x 14cm (approximately 0.02m) for bioprocessing systems with volumes from 5L to 1000L 2 ) to 1.1m x 1.1m (approx. 1.2m 2 ) (50% reduction), or approximately 11 cm x 11 cm (approximately 0.01 m) for bioprocessing systems with volumes from 5 L to 1000 L. 2 ) to 85cm x 85cm (approx. 0.8m 2 ) (70% reduction).

[0024] Thus, embodiments of the present invention may provide a bioprocessing system with a reduced footprint for bench systems and larger cleanroom-based systems. For example, it may be possible to reduce the footprint from 2.1 m x 1.3 m for the system and 1.1 m x 0.61 m for the pump cart to 1.1 m x 1.1 m for the system, or even for both the system and pump cart together. Such smaller size and footprint systems are also easier to move, fit through smaller doors, and integrate into smaller cleanroom modules. Another advantage of the reduced holdup volume and reduced footprint provided by the bioprocessing system according to the present invention is that less cleanroom space is required compared to prior art bioprocessing systems. Therefore, drug / product manufacturing costs can be reduced, as cleanroom space is expensive.

[0025] Another advantage of the reduced footprint and hold-up volume is that the bioprocessing system according to the invention improves the integration and connection of multiple unit operations and systems into complete processing trains and manufacturing setups. Bioprocessing systems as described thus far represent a single unit operation, and with the example of a separation or fluid handling system, this system is typically connected to other equipment upstream and downstream of the unit operation. In stand-alone unit operations and processing setups, typically associated with batch processing of drug substances, inlet and outlet tanks for supplying and receiving fluids may be connected. The bioprocessing system according to the invention provides the mentioned advantages of reduced hold-up volume, footprint, and processing space, as already described. In another embodiment, a bioprocessing system according to the invention may be part of a connected and / or continuous process setup, in which at least two unit operations and / or bioprocessing systems, normally set up for different processing operations, are interconnected, thereby providing a more or less continuous manufacturing setup and processing of a product that increases overall process efficiency, reduces processing time, reduces footprint, and / or eliminates intermediate fluid holding tanks that would otherwise be required when running the process in sequential and separated batch process setups, the latter corresponding to moving the product (active ingredient) through a series of separated and contained unit operations that may even be physically run in different facilities and / or clean rooms. Thus, a bioprocessing system according to the invention improves process efficiency and reduces footprint in both batch-processing connected processing setups and batch-processing (semi-)continuous processing setups.

[0026] In another embodiment of the invention, the bioprocessing system is compartmentalized into a fluid processing portion and a control system portion, and the control system portion may be located outside the floor space and processing footprint of the fluid processing system, outside the footprint of the clean room containing the fluid processing system. In one example, the system control portion, including electrical, pneumatic, or electronics arrangements such as sensor transmitters, pump drive controllers, valve controllers, bus systems, control computers, processors (PLCs), etc., may be separated from the fluid flow path and located in a separate cabinet in the same clean room, thereby not interfering with the footprint of the fluid processing setup, or may be located outside the clean room in an adjacent, typically non-secure room. An optional wall between the fluid processing portion and the control system portion may include cables and connectors for connecting the fluid processing portion and the control system portion. A portion of the system may be located in the cloud, i.e., a computing means for achieving control and analysis of processing systems and processes.

[0027] Another advantage of the bioprocessing system according to the present invention, which provides a low holdup volume, is that necessary cleaning procedures can be carried out with greater efficiency and with a smaller required fluid volume. For cleaning, harsh, aggressive cleaning fluids, such as caustic or oxidizing agents, are typically employed. These fluids are costly both in production and disposal, as well as in extensive cleaning after cleanup operations become necessary. The reduced fluid volume required by the system according to the present invention thereby reduces the cost and environmental footprint associated with requiring less energy, as well as the consumption of natural resources such as water. It should be noted that the water required for bioprocessing must be pretreated by reverse osmosis or distillation, thereby requiring high labor and energy consumption to obtain the WFI (water for injection) quality required for use in bioprocessing.

[0028] Beyond its low holdup volume, the bioprocessing system according to the present invention also improves purification efficiency. This is achieved by a compact design with low holdup volume, requiring less purification fluid volume. Furthermore, this is achieved by a system design with vertically arranged fluid paths, thereby avoiding air trapped within the fluid paths, which would otherwise require flushing with excess fluid volume. Air trapped within components can limit access of cleaning fluid to all internal surfaces of the fluid flow path, thereby limiting cleaning efficiency. For example, air can enter the inlet of the processing system when changing or reconnecting a container. However, air can also arise during processing due to degassing of the fluid, which leads to the slow accumulation and development of air pockets within the flow path, provided the flow path is not optimized and has a sufficient physical inclination relative to the horizontal axis of the flow direction such that the air is carried toward the system's outlet, thereby starving the system of air.

[0029] Further, according to some embodiments of the present invention, the flow path 3 is provided as, at least to some extent, a self-supporting flow path 3. In some embodiments of the present invention, additional support structures are also provided, for example, as a support frame as described in connection with FIGS. 2 and 3 or as a support spine as described in connection with FIG. 5. However, in some embodiments of the present invention, the flow path 3 may be provided as a completely self-supporting structure. This may be achieved by printing the flow path 3 with an appropriate thickness and using an appropriate material. The thickness may vary for different portions of the flow path. Furthermore, in some embodiments of the present invention, printing the flow path 3 with a 3D printer may include printing some support structure outside of the flow path 3 to provide additional support.

[0030] As shown in Figure 2b, all inlets and outlets 7, 9, 11 may be located on the same side of the bioprocessing system 1. However, other arrangements of inlets and outlets are of course possible.

[0031] 2a-2d, a bioprocessing system 1' according to one embodiment of the present invention is shown in different perspective views. The bioprocessing system 1' is almost identical to the bioprocessing system 1 as described in connection with FIGS. 1a-1d. However, the bioprocessing system 1' further comprises a support structure 31 in the form of a partially enclosing frame. The flow path 3 may be connected to and supported by the support structure 31. Furthermore, the support structure 31 may comprise a user interface 33 for controlling the bioprocessing system 1'. In this embodiment of the present invention, the user interface 33 is provided on one side of the support structure 31, and inlet and outlet fluid connections 35a, 35b to the inlet 7 and outlet 11 of the flow path 3 are provided on the opposite side.

[0032] In Figures 3a and 3b, the bioprocessing system 1' as shown in Figures 2a-2d includes doors 41a, 41b. The doors may be preferably openable either by sliding upward or by being hinged on one side and swinging outward. The doors 41a, 41b may be transparent.

[0033] The flow path 3 shown in FIGS. 1a-1d can be produced in one or more sections using a 3D printer. In FIGS. 4a-4d, the fluid path 3 shown in FIGS. 1a-1d is shown separated into two sections: an upper fluid path section 3a and a lower fluid path section 3b. Perspective views from the first and second sides are shown in FIGS. 4a-4d. The fluid path 3 can also be produced in one single piece or in more than two pieces using a printer. The flow path 3 includes multiple inlets 7, at least one bioprocessing device inlet connection 9a, at least one bioprocessing device outlet connection 9b, and multiple outlets 11, as described above. The flow path 3 further includes flow path portions 5a', 5b', 5c', 5d', 5e' of the active components provided in the bioprocessing system 1, as described above, and the fluid paths between these described components. The entire flow path 3, or at least a portion of the flow path 3, may be preferably fabricated by a 3D printer, as described above. Some parts of the flow path 3 may possibly be produced by other methods.

[0034] The present invention allows separate sections of the flow path 3 to be provided to be connected when assembling the bioprocess system 1. This may allow different types of sections to be combined in different ways, thereby providing different types and sizes of systems. For example, different numbers of inlets and outlets may be provided within the sections.

[0035] 5 shows a schematic diagram of a portion of a bioprocessing system 101 according to one embodiment of the present invention, where a support structure 131 is provided vertically in the middle of the bioprocessing system 101 as a support spine. The flow path 103 is provided around the support structure 131, and the active portion 105a'' of the active component 105 is mounted around the flow path 103 and is easily accessible from the outside of the bioprocessing system 101. Cables 106 for electrical or pneumatic control of the active component may be provided inside the support structure 131. [Explanation of symbols]

[0036] 1. Bioprocess system, bioprocessing system 1' Bioprocess System 3 Flow path, fluid path 3a Flow path, upper fluid path section 3b Flow path, lower fluid path section 5a Active components, valves, pumps 5b Active component, inlet valve 5c Active components, valves, bioprocessing device valves 5d Active components, valves, outlet valves 5e Active Components, Sensing Components 5a', 5b', 5c', 5d', 5e' Flow path parts 5a'' Active part, driving part 5b'' Active part, operating part 5c'' Active part, working part 5d'' Active part, working part 5e'' Active part, sensing part 7 Entrance 9a Bioprocessing device inlet connection 9b Bioprocessing device outlet connection 11 Exit 21 Filter 23 Bubble Trap 25 valves 31 Support structure 33 User Interface 35a inlet fluid connection 35b outlet fluid connection 101 Bioprocess Systems 103 Flowpath 105 Active Components 105a'' active part 106 Cable 131 Support structure

Claims

1. A bioprocessing system (1), comprising: Multiple entrances (7), at least one bioprocessing device inlet connection (9a) and at least one bioprocessing device outlet connection (9b); Multiple exits (11), and Flow path portions (5a', 5b', 5c', 5d', 5e') of at least some active components (5a, 5b, 5c, 5d, 5e) included in the bioprocessing system a flow path (3, 3a, 3b) comprising: an active part (5a'', 5b'', 5c'', 5d'', 5e'') of said active component (5a, 5b, 5c, 5d, 5e); Equipped with The flow paths (3, 3a, 3b) of the bioprocess system (1) are positioned substantially centrally and in a substantially vertical orientation within the bioprocess system (1), whereby the active portions (5a'', 5b'', 5c'', 5d'', 5e'') are positioned around the flow paths (3, 3a, 3b) that are accessible from outside the bioprocess system (1) and each connect with a corresponding flow path portion (5a', 5b', 5c', 5d', 5e') of the active components (5a, 5b, 5c, 5d, 5e).

2. 10. The bioprocessing system of claim 1, wherein the flow path is 3D printed in several sections or in one section.

3. 3. The bioprocessing system (1) according to claim 1 or 2, wherein the flow paths (3, 3a, 3b) are at least partially self-supporting.

4. 4. The bioprocess system (1) of claim 1, wherein the flow paths (3, 3a, 3b) are 3D printed with a thickness configured to make the flow paths at least somewhat self-supporting, which thickness may vary for different portions of the flow paths, and / or the flow paths are 3D printed with additional external support structures.

5. 5. The bioprocessing system (1) according to claim 1, wherein the active components (5a, 5b, 5c, 5d, 5e) comprise several valves (5b, 5c, 5d) and possibly further one or more pumps (5a) and one or more sensing components (5e).

6. 6. The bioprocessing system (1) according to any one of claims 1 to 5, wherein the flow paths (3, 3a, 3b) are 3D printed from corrosion-resistant metal.

7. 7. The bioprocessing system (1) according to any one of claims 1 to 6, further comprising a support structure (31, 131) comprising a central spine (131) disposed inside the flow path (103) or a frame (31) partially surrounding the flow path (3, 3a, 3b), and comprising a user interface (33) and tubing connections (35a, 35b).

8. 8. The bioprocessing system (1) according to any one of claims 1 to 7, having a footprint ranging from about 17 cm x 17 cm to about 1.3 m x 1.3 m for bioprocessing systems having a capacity between 5 L and 1000 L, a footprint ranging from about 14 cm x 14 cm to about 1.1 m x 1.1 m for bioprocessing systems having a capacity between 5 L and 1000 L, or a footprint ranging from about 11 cm x 11 cm to about 85 cm x 85 cm for bioprocessing systems having a capacity between 5 L and 1000 L.

9. Approximately 0.03 m for bioprocess systems with volumes between 5 L and 1000 L 2 Approximately 1.7m from 2 footprint ranging from approximately 0.02 m for bioprocessing systems with volumes ranging from 5 L to 1000 L 2 Approximately 1.2 m from 2 footprint in the range of 0.01 m for bioprocessing systems with volumes between 5 L and 1000 L. 2 Approximately 0.8 m from 2 9. The bioprocessing system (1) according to any one of claims 1 to 8, having a footprint in the range of

10. 10. The bioprocessing system of claim 1, wherein the flow paths are at least partially 3D printed, resulting in a parts replacement ratio of >2:1, >3:1, >5:1, or >10:1.

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