A bioprocessing system

Abstract

A method (1000) and a bioprocessing system is disclosed. The bioprocessing system comprises a plurality of bioprocessing stations (100), each configured to perform a respective bioprocessing operation on a feed comprising a mixed liquid and a sample. The system further comprises a liquid supply apparatus (200) comprising a valve arrangement (210), a conduit (220), a mixing arrangement (230), and a controller (240). The mixing arrangement (230) is configured to supply at least a first solution component and a second solution component to the conduit (220), thereby forming a mixed liquid. The valve arrangement (210) is operable to selectively supply the mixed liquid to each of the bioprocessing stations (100), and the controller (240) is configured to, for each bioprocessing station (100), control the operation of the mixing arrangement (210) such that the mixed liquid comprises a predetermined set of characteristics associated with the bioprocessing operation of said bioprocessing station (100).

Description

[0001] A BIOPROCESSING SYSTEM

[0002] Technical Field

[0003] The present disclosure relates to manufacturing of biopharmaceutical products, and more specifically to bioprocessing systems and methods for performing one or more bioprocessing operations on a feed.

[0004] Background

[0005] Bioprocessing operations, such as filtration and chromatography, play an important role in the biopharmaceutical industry. The bioprocessing operations are typically performed to separate and purify proteins, vaccines, and other components from complex bioreactor mixtures. The target material, i.e., the product of interest to separate or purify, may be provided in a liquid flow, or feed, comprising a mobile phase moving the target material through the bioprocessing system. The mobile phase often includes a mixed liquid, such as a buffer solution, having well-defined characteristics such as pH and conductivity, suitable for the relevant bioprocessing operation.

[0006] The biopharmaceutical processing puts high demand on biosafety and cleanliness to prevent loss of biological integrity, for example through release of harmful chemicals to the environment, as well as product contamination by particulate matter and microorganisms. Biopharmaceutical manufacturing therefore requires relatively complex and expensive cleanroom facilities.

[0007] Many bioprocessing systems involve single-use components to reduce the need for cleaning and sterilising. Certain single-use components may be provided as disposable flow kits having disposable tubing carrying the liquid flow to the bioprocessing component performing the bioprocessing operation. The flow kit may be replaced between each bioprocessing operation or sample batch.

[0008] In the general strive for reduced costs and improved production, there is a need for improved technologies allowing for a more efficient use of the bioprocessing equipment and the facilities used for the processing.

[0009] Summary

[0010] According to a first aspect of the present disclosure, there is provided a bioprocessing system for separating a target material of a feed from one or more impurities. The system comprises a plurality of bioprocessing stations, wherein is each configured to perform a respective bioprocessing operation on the feed. The plurality of bioprocessing stations are interconnected such that an outlet of a first one of the plurality of bioprocessing stations is connected to an inlet of a next one of the plurality of bioprocessing stations. The system further comprises a liquid supply apparatus comprising a valve arrangement, a conduit, a mixing arrangement, and a controller, wherein the mixing arrangement is configured to supply at least a first solution component and a second solution component to the conduit to form a mixed liquid. The valve arrangement is fluidically connected to the conduit and operable to selectively supply the mixed liquid to each of the bioprocessing stations. The controller is configured to, for each bioprocessing station, control the operation of the mixing arrangement such that the mixed liquid comprises a predetermined set of characteristics associated with the bioprocessing operation of the bioprocessing station. At least two of the plurality of bioprocessing stations (e.g. all of them), may be configured to perform a respective different bioprocessing operation on the feed (e.g. consecutively / in series as at least part of an overall separation process).

[0011] According to a second aspect, there is provided a method for separating a target material of a feed from one or more impurities. The method comprises supplying the feed to a plurality of bioprocessing stations as outlined above in connection with the first aspect, mixing, in a mixing arrangement, at least a first solution component and a second solution component to form a mixed liquid, and selectively supplying the mixed liquid to each of the plurality of bioprocessing stations. For each of the plurality of bioprocessing stations, the mixing arrangement is operated to provide the mixed liquid with a predetermined set of characteristics associated with the bioprocessing operation performed by said bioprocessing station.

[0012] The liquid supply apparatus makes it possible to provide the mixed liquid, such as a buffer solution, directly to the bioprocessing stations without the need for any intermediate storage or manual handling of the mixed liquid. Conventional preparation of the mixed liquid typically requires a number of operations including manual handling and transfer of raw material, solution preparation, mixing, and cleaning of the equipment involved. Once prepared, the mixed liquid requires a place where it can be stored until it is used for the bioprocessing operation. Conventional preparation and handling of the mixed liquid is therefore often a timeconsuming and logistically challenging process that requires planning as well as ample facility footprint. The present disclosure offers a solution in which the mixed liquid instead may be delivered on-demand and directly to the bioprocessing stations. Each mixed liquid may be prepared from water for injection (WFI) and one or more single-component stock solutions, and the liquid supply apparatus may be operable to prepare a mixed liquid with a predetermined set of characteristics matching the requirements associated with a specific bioprocessing operation. The outlet(s) of the liquid supply apparatus may be directly connected to one or more bioprocessing stations to allow the mixed liquid to be supplied on-demand, without the need for intermediate storage or manual transporting of the mixed liquid. This way of preparing the mixed liquid may be referred to as in-line conditioning. In some examples, each of the bioprocessing stations may be configured to request and receive a mixed liquid from the mixed liquid apparatus.

[0013] The bioprocessing stations may be interconnected such that the outlet of a first one of the bioprocessing stations is connected to the inlet of a next one of the bioprocessing stations. The bioprocessing stations may hence be arranged in a cascade configuration, in which a feed, comprising biological target compounds and / or impurities, can be subjected to several bioprocessing steps uninterruptedly thanks to being continuously passed through the bioprocessing stations. Several chromatography devices and / or filter devices, for example, may be connected in-line, within the bioprocessing system. Traditionally, purification process flows are typically interrupted due to manual changing of buffers and / or chromatography devices within the system, and due to some steps (such as conditioning of chromatography media and certain filtration / purification steps) being performed in separate containers or devices outside of the chromatography system. With the presently disclosed bioprocessing system, less human intervention is required, and the processing time may be reduced compared to when operating previously known bioprocessing systems.

[0014] The valve arrangement allows for the liquid supply apparatus to supply two or more of the bioprocessing stations with the mixed liquid required for their respective bioprocessing operation. Each of the bioprocessing stations may be provided with a mixed liquid having a set of characteristics associated with that specific bioprocessing station. Hence, a single liquid supply apparatus can be used for supplying a plurality of bioprocessing stations or linked / co- located production facilities with one or more types of mixed liquids, thereby allowing for a more efficient use of the liquid supply apparatus.

[0015] Further, the mixed liquid apparatus may be used to drive the flow of mixed liquid through the bioprocessing system, thereby eliminating the need for dedicated pumps in each of the bioprocessing stations and allowing for a simplified design of the bioprocessing stations. Removing the mixed liquid pumps from the bioprocessing stations may save space and simplify the electrical infrastructure, as there is no need for providing the bioprocessing stations with any power supply for the mixed liquid pumps.

[0016] The liquid supply apparatus may comprise a control sensor arrangement, comprising a sensor such as a pH sensor, a conductivity sensor, or a flow sensor for controlling the corresponding characteristics of the mixed liquid supplied to the bioprocessing stations. Accordingly, there is a reduced need for sensors in the bioprocessing stations. The sensor(s) may be used as a control sensor arrangement configured to output a signal indicating a characteristic of the mixed liquid and which can be used as feedback in controlling the operation of the mixing arrangement of the liquid supply apparatus.

[0017] In some examples, each of the bioprocessing stations may comprise an inlet valve arrangement to control the supply of mixed liquid or sample to the bioprocessing station. The inlet valve arrangement may for example be arranged to bypass the bioprocessing component, such as a chromatography column or filter, in case the mixed liquid does not have the desired characteristics or during a cleaning step, and to direct the mixed liquid and the sample to the bioprocessing component to initiate the bioprocessing operation.

[0018] In further examples, each of the bioprocessing stations may comprise a release valve arrangement configured to control release of feed or mixed liquid from the bioprocessing station. The release valve arrangement may, for example, be operable to direct the feed either to a waste outlet, or to the inlet of another bioprocessing station.

[0019] The valve arrangement(s) may be employed to control fluid flows through the bioprocessing stations during different phases of the bioprocessing operations, such as an equilibration phase, a column loading phase, an elution phase, and a regeneration phase (in case of the bioprocessing component being, e.g., a chromatography column). In an example, the inlet valve arrangement may be operated to supply the mixed liquid to a bioprocessing station during the equilibration phase, the elution phase and the regeneration phase, and to supply the sample to the bioprocessing station during a sample loading phase. In a further example, the release valve arrangement may be operated release an output from the bioprocessing station to a waste outlet during the equilibration phase, the sample loading phase, and the regeneration phase, and to release the output to the next one of the bioprocessing stations during the elution phase. According to a third aspect, there is provided a bioprocessing system operable to perform a plurality of bioprocessing operations on a liquid flow comprising a mixed liquid carrying a sample. The bioprocessing system comprises a bioprocessing component operable to perform at least one of the bioprocessing operations on the liquid flow, a pump unit operable to drive a flow of the mixed liquid through a tubing system to the bioprocessing component, and a sample supply operable to add the sample to the flow of the mixed liquid at a position between the pump unit and the bioprocessing component, thereby forming the liquid flow. The tubing system is a disposable tubing system configured to be replaced between each of the plurality of bioprocessing operations and the pump unit is a reusable pump unit operable to be reused for each of the plurality of bioprocessing operations.

[0020] According to a fourth aspect, a tubing system for a bioprocessing system as outlined above in connection with the third aspect is provided. The tubing system comprises a mixed liquid inlet configured to be coupled to the pump unit, an outlet configured to be coupled to the bioprocessing component, a conduit configured to convey a flow of the mixed liquid from the pump unit to the bioprocessing component, and a sample inlet configured to supply the sample to the flow of the mixed liquid, the sample inlet being arranged between the mixed liquid inlet and the outlet. The tubing system is a disposable tubing system configured to be replaced between each of the plurality of bioprocessing operations.

[0021] A disposable, or single-use, tubing system is generally understood as a tubing system designed for a single batch or a single production cycle. After use, the tubing system can be disposed of rather than being cleaned and sterilised for reuse. The tubing system may come pre-sterilised to eliminate the need for complex and time-consuming processes on-site and may comprise one or more sterile filters, barriers, or connectors arranged at inlets of the tubing system to maintain a sterility of the tubing system prior to use. Using each tubing system only once reduces the risk of cross-contamination between batches as well as the time needed for cleaning, sterilisation and validation of reusable equipment. Typically, the tubing system may be formed of plastic derivatives or other materials suitable for single use, which are relatively cheap. Upfront costs may therefore be reduced compared to investing in permanent, stainless- steel systems.

[0022] Accordingly, a reusable pump unit refers to a pump unit designed to be used multiple times for the same or different production batches or production cycles. Although the initial investment may be higher, reusable pump units can be more cost-effective over the long term due to their extended use. Further, a reusable pump unit may generate less waste compared to disposable pump units, making the reusable pump unit a more environmentally sustainable option.

[0023] The third and fourth aspects outlined above allow for the benefits of single-use components to be combined with the benefits of reusable components. While the disposable tubing system reduces the need for cleaning and sterilising of those parts, the reusable pump unit allows for the costs of the disposable material and the waste to be reduced. By adding the sample at a position downstream the pump unit, i.e., at a position between the pump unit and the bioprocessing component, the risk for the pump unit coming into contact with the sample can be reduced. This can be contrasted with conventional bioprocessing systems in which the pump unit, or at least a pump head of the pump unit, is included in the disposable flow kit and thereby needs to be replaced with the rest of the flow kit. By separating the pump unit from sample-containing parts of the liquid flow, there is a reduced need for replacing the pump unit between different bioprocessing operations or sample batches.

[0024] To further reduce the risk of the pump unit coming into contact with the sample, a protection valve may be arranged between the pump unit and the position in which the sample is supplied to the mixed liquid. The protection valve may be operable to prevent the sample from reaching the pump.

[0025] Further, by separating the pump unit from the disposable tubing system, the pump unit may be arranged at a separate location, which may hold a lower grade of cleanliness than the area in which the bioprocessing operation is performed. The bioprocessing component may, for example, be arranged in processing area maintaining a first grade of cleanliness and the pump unit in a service area maintaining a second, lower grade of cleanliness. In this way, the footprint of the equipment arranged in the processing area may be reduced and the costs for maintaining the higher grade of cleanliness reduced accordingly.

[0026] It will be appreciated that the bioprocessing system of the third aspect may comprise one or more bioprocessing components, which may be cascade connected in a configuration similar to the one discussed above in connection with the first and second aspects. Further, a bioprocessing station according to the first aspect may comprise or be used with a tubing system according to the fourth aspect outlined above.

[0027] As used in the present disclosure, the term “bioprocessing station” typically refers to a processing unit comprising at least one of a chromatography column, a filter, and a mixer. Other bioprocessing components or devices are however also possible. The bioprocessing operation performed by a chromatography column, a filter, or a mixer may be referred to as a unit operation.

[0028] The target material may be understood as the product of interest to separate or purify. The target material may, for example, include biological target materials such as proteins, vaccine components, antibodies, and biomolecules. The target material is typically provided as a sample, comprising the target material and one or more impurities.

[0029] The target material is carried by a mobile phase, which typically comprises the mixed liquid that drives the target material through the bioprocessing system.

[0030] By “feed” is, in the context of the present disclosure, generally understood the input to / output from a bioprocessing component. Hence, the feed may or may not comprise the target material and any impurities, depending on the actual bioprocessing operation.

[0031] The mixed liquid may typically be a buffer liquid, or buffer solution. The buffer solution may be prepared from one or more buffer substances, such as a first buffer substance and a second buffer substance mixed with water for injection. In this context, the liquid supply apparatus may be referred to as a buffer stock blending system.

[0032] The term “conduit” may typically be understood as a portion of tubing connecting two elements of a flow path or a flow circuit. Typically, the conduit forms the portion of tubing conveying the mixed liquid to the bioprocessing component. It may be possible for this portion to comprise a unique tube or several tubes, possibly having different diameters, connected in series or in parallel.

[0033] A bioprocessing station may comprise a base unit, also referred to as a skid, onto which at least one of the bioprocessing component and the tubing system can be releasably mounted. The base unit may provide a self-contained, modular unit that can be transported and integrated into a larger processing system. In some examples, the base unit may comprise one or more of the above valve arrangements, such as a protection valve, an inlet valve, or a release valve. A valve arrangement may, for example, comprise a valve actuator operable to releasably engage a conduit of a tubing system (such as the one discussed above in connection with the fourth aspect) to form a pinch valve controlling the flow of the mixed liquid through the tubing system.

[0034] The bioprocessing system may comprise one of more sensor arrangements operable to output a signal indicative of a characteristic of the mixed liquid or the liquid flow passing through the system. The sensor arrangement may comprise at least one of a pH sensor, a conductivity sensor, and a sample sensor. In some examples, the sensor arrangement may be arranged upstream of the position in which the sample is added to the flow of the mixed liquid and configured to measure at least one of a pH level and a conductivity level of the mixed liquid. In some examples, the sensor arrangement is arranged in the disposable tubing system, and in some examples the sensor arrangement is arranged in a reusable portion associated with the pump unit.

[0035] In some examples, a sensor is provided, which is operable to generate a signal indicating a concentration or amount of the sample in the liquid flow. Examples of such sensor include UV sensors configured to measure specific target materials in the liquid flow. The sensor may be arranged upstream the processing component to measure a concentration or amount of target material supplied to the processing component, or downstream the processing component to measure a concentration or amount of target material leaving the (or being bypassed) the processing component.

[0036] In some examples, the sensor measuring the sample concentration is included in the disposable tubing system, whereas the pH sensor and the conductivity sensor are arranged in the reusable part of the bioprocessing system.

[0037] The bioprocessing operations often require a cleanroom environment with a relatively high degree of biosafety and cleanliness to prevent product contamination by particulate matter and microorganisms. Maintaining a certain grade of cleanliness is typically associated with costs, which tends to increase with increasing cleanliness level. To reduce the volume of highly controlled areas and hence the costs for maintaining such a high grade of cleanliness, cleanroom facilities commonly comprise different areas maintained at different grades of cleanliness. For the purpose of the present disclosure, cleanroom areas maintained at a higher grade of cleanliness may be referred to as processing areas, whereas cleanroom areas maintained at a lower grade of cleanliness may be referred to as service areas. In more general terms, these respective areas may be referred to as a first area and a second area maintained at a first grade of cleanliness and a second grade of cleanliness, respectively.

[0038] In some examples, the plurality of bioprocessing stations according to the first and second aspects may be arrangeable in the processing area, whereas the mixing arrangement may be arrangeable in the service area. In further examples, the pump unit according to the third and fourth aspects may be arrangeable in the service area, whereas the tubing system and the processing component may be arranged in the processing area. By moving some components of the system, such as the mixing arrangement or the pump unit, to the less clean area, the footprint of the equipment in the cleaner area can be reduced. This, in turn, allows for the volume of the cleaner area to be reduced.

[0039] In a further aspect, a method for reconfiguring a bioprocessing system according to the third aspect is provided. In the method, the bioprocessing system is reconfigured between two consecutive bioprocessing operations. The reconfiguring comprises disconnecting a first tubing system from the pump unit, the bioprocessing component, and the sample supply, and connecting a second tubing system to the pump unit, the bioprocessing component, and the sample supply. Each of the first and second tubing systems is similarly configured as the tubing system according to the fourth aspect and thus operable to convey the flow of the mixed liquid from the pump unit to the bioprocessing component.

[0040] Brief Description of the Drawings

[0041] Further features and advantages of the above aspects will become apparent from the following description of preferred embodiments, given by way of example only, which is made with reference to the accompanying drawings.

[0042] Figure 1 shows a schematic diagram of a bioprocessing system according to an example.

[0043] Figure 2 shows a schematic diagram of a bioprocessing system according to another example.

[0044] Figure 3 is a flow chart outlining a method for operating a bioprocessing system according to an example.

[0045] Figure 4a is a schematic diagram of a bioprocessing system according to an example.

[0046] Figure 4b is a tubing system for a bioprocessing system as shown in figure 4a.

[0047] Figure 5a shows the tubing system mounted onto a base unit.

[0048] Figure 5b shows a bioprocessing system according to an example, wherein the base unit is arranged in processing area and the mixed liquid pump unit is arranged in a service area.

[0049] Detailed Description

[0050] Figure 1 is a schematic diagram of a bioprocessing system according to an example, operable to separate a target material of a feed from one or more impurities. The system comprises a plurality of bioprocessing stations 100, each configured to perform a respective bioprocessing operation on the feed. The bioprocessing stations are interconnected such that an outlet 112 of a first one 110 of the bioprocessing stations is connected to an inlet 121 of a next one 120 of the bioprocessing stations. In different words, the bioprocessing stations 110, 120, 130 shown in figure 1 may be arranged in a cascade connection, in which the output from one of the stations is fed to the inlet of the next station.

[0051] In the present, exemplary configuration, a sample comprising a target material and one or more contaminants, for example provided from a bioreactor mixture, is fed from a sample supply 20 to a sample inlet 111 of the first bioprocessing station 110. Here, the sample is mixed with mixed liquid, such as a buffer, prepared by the liquid supply apparatus 200 and which is employed to drive the sample through a bioprocessing component of the bioprocessing station 110. The liquid supply apparatus 200 may thus drive the flow of the mixed liquid and the sample without the use of any dedicated mixed liquid pump, such as the pump unit 320 shown in figures 4a and 5b). The mixed liquid may have a first set of characteristics, such as pH and conductivity levels, associated with the bioprocessing operation and be supplied to the first bioprocessing station 110 via mixed liquid inlet 113. The output from the first bioprocessing station 110 may then be supplied from the feed outlet 112 of the first bioprocessing station 110 to the feed inlet 121 of the second bioprocessing station 120, where it is mixed with mixed liquid having a second set of characteristics prepared by the mixing arrangement 210 and provided to the second bioprocessing station 120 via mixed liquid inlet 123. Thereafter, the output from the second bioprocessing station 120 is supplied from the feed outlet 122 of the second bioprocessing station 120 to the feed inlet 131 of the third bioprocessing station 130. In the third bioprocessing station 130, the feed is mixed with mixed liquid having a third set of characteristics prepared by the mixing arrangement 210 and provided to the third bioprocessing station 130 via mixed liquid inlet 133. The output from the third bioprocessing station 130 may, as indicated in figure 1, be output from the feed outlet 132 to a storage tank 30. It will be appreciated that in the context of the present disclosure, the output from each of the bioprocessing stations 110, 120, 130 will be referred to as “feed”.

[0052] The liquid supply apparatus 200 is operable to supply the bioprocessing stations 100 with a mixed liquid required for the respective bioprocessing operations performed by the bioprocessing stations 100. The liquid supply apparatus 200 is fluidically connected to each of the bioprocessing stations 100 indicated in figure 1 and comprises a valve arrangement 210 configured to selectively supply the mixed liquid to each of the bioprocessing stations. As will be discussed in further detail in connection with figure 2, the valve arrangement 210 may be operable to supply the bioprocessing stations 100 in sequence, i.e., one at a time, or two or more at the same time. The liquid supply apparatus 200 further comprises a conduit 220 connecting the valve arrangement 210 to a mixing arrangement 230 configured to supply at least a first solution component and a second solution component to the conduit 210 to form the mixed liquid. The first and second solution components may be retrieved from a respective component supply 10. In an example, the mixed liquid is a buffer solution formed from a first solution component being an acidic buffer component, a second solution component being a basic buffer component, and water-for-inj ection (WFI). The buffer solution may, for example, be prepared from a weak acid and a weak base, a weak acid and a strong base, or a weak base and a strong acid. Exemplary buffer liquid that may be prepared using the liquid supply apparatus 200 include phosphate, acetate, citrate, tris, and bis-tris buffers. It will be appreciated that further inlets may be provided, as indicated in figure 1 and discussed in further detail in connection with figure 2.

[0053] Figure 1 illustrates a configuration in which the liquid supply apparatus 200 supplies a single production arrangement, i.e., a production line comprising a plurality of bioprocessing stations 100 interconnected for the production of a specific product or target material. However, it will be appreciated that the liquid supply apparatus 200 as disclosed herein may be arranged to supply two or more production lines, each comprising a plurality of interconnected bioprocessing stations 100 for the production of a respective product or target material. Thus, a single liquid supply apparatus 200 according to the present disclosure may be operable to supply two or more production lines with mixed liquid.

[0054] A controller 240 is provided to control the operation of the liquid supply apparatus 200, and more specifically the operation of the mixing arrangement 230, such that the mixed liquid comprises a predetermined set of characteristics associated with the bioprocessing operation performed by the bioprocessing station supplied with the mixed liquid. The characteristics typically refer to pH and conductivity, which may be determined and adjusted by varying the relative proportions of the solution components mixed by the mixing arrangement 230.

[0055] The characteristics may be determined based on sensor signals from a control sensor arrangement (not shown in figure 1) and used as corrective feedback to the controller 240 to assist in achieving, for instance, the desired pH level or conductivity level. The controller 240 may further be arranged to control the operation of the valve arrangement 210 to determine which of the bioprocessing stations 100 is going to be supplied with the mixed liquid. The controller 240 is communicatively connected to the mixing arrangement 230 and the valve arrangement 210, for example by a wired or wireless connection.

[0056] Figure 2 is a schematic diagram of a bioprocessing system according to an example, which may be similarly configured as the bioprocessing system in figure 1. The exemplary system comprises a plurality of bioprocessing stations 100, including a capture station 110, a normal flow filtration (NFF) station 120, and a polishing station 130. A further bioprocessing station is disclosed in figure 2, which is a virus inactivation station 140 arranged between the capture station 110 and the NFF station 120. In the following, each of these exemplary bioprocessing stations will be discussed in further detail.

[0057] Starting with the capture station 110, this may be the first part of the downstream processing performed by the plurality of bioprocessing stations 100 shown in figure 2. In this station, the target material may be purified from a complex mixture, typically coming from a bioreactor or fermentation broth. The capture step may be designed to separate the target material, or product of interest (like a protein, antibody, or enzyme) from a majority of impurities present in the crude mixture. The bioprocessing operation typically involves selective binding of the target molecule to a medium, such as a resin in a chromatography column.

[0058] The sample, comprising the target material, is provided in a target supply 20, which may be a mixer or tank connected to the sample inlet 111 of the capture station 110. A sample pump 21 is provided to drive a flow of the sample to an inlet valve 116, which may be operable to control a release of sample and mixed liquid from the mixed liquid inlet 113 to the bioprocessing component 115, which in the present example is a chromatography column 115. The output from the chromatography column 115 is supplied to a release valve 117, which is operable to selectively release the output feed to a waste outlet 114 or a feed outlet 112.

[0059] The feed outlet 112 of the capture station 110 is coupled to the virus inactivation station 140, which comprises a first and a second mixer for exposing the target material for a pH treatment for virus inactivation. The output from the capture station 110 may first be supplied to the first mixer 141 where the target material is exposed to an acid, and then to the second mixer 142 where the target material is neutralised by a base. The acid and the base may be provided from a respective single-use container 143, 144 as indicated in figure 2, or from the liquid supply apparatus 200.

[0060] The output from the virus inactivation station 140 may then be supplied to the feed inlet 121 of the NFF station 120 for a filtration operation. The feed inlet 121 is connected to an inlet valve 126, which is operable to mix the target material of the feed with a liquid mixture received at the mixed liquid inlet 123 of the NFF station 120 and release the feed to the bioprocessing component 125, which in this case may be a depth filter 125. The output from the depth filter 125 may then be supplied to a release valve 127, which is operable to release the feed to a waste outlet 124 or a mixer 128.

[0061] The output of the mixer 128 may be supplied to a feed inlet 131 of the polishing station 130, which may be configured to perform a further purification and refining of the target material to meet the desired quality specifications. The polishing station 130 may thus comprise a chromatography column designed to remove any remaining impurities, such as host cell proteins, DNA, viruses, or target material-related impurities like aggregates or variants of the target material. Similar to the capture station 110 and the NFF station 120, the polishing station 130 may comprise an inlet valve 136 operable to regulate and control the flow of target material from the feed inlet 131 and mixed liquid from the mixed liquid inlet 133 to the bioprocessing component 135. A feed pump 22 may also be provided to drive a flow of the feed from the feed inlet 13 Ito the bioprocessing component 135. Further, a release valve 137 may be provided to receive the output from the bioprocessing component 135 to a waste outlet 134 or a feed outlet, which in turn may be connected to a mixer 138.

[0062] As indicated above, one or more of the bioprocessing stations 110, 120, 130, 140 may be fluidically coupled to the liquid supply apparatus 200 for supply of mixed liquid to be used in the operation of the bioprocessing operations performed by the bioprocessing station(s). In the present example, each of the capture station 110, NFF station 120, and the polishing station 130 may be coupled by a respective conduit to the liquid supply apparatus 200. These bioprocessing stations and their respective bioprocessing operations are described to illustrate the benefits with the liquid supply apparatus 200 and the in-line condition it enables. It will be appreciated that the liquid supply apparatus 200 and the plurality of bioprocessing stations 110 can be used in other configurations to perform other types of bioprocessing operations.

[0063] The liquid supply apparatus 200 comprises a mixing arrangement 230 operable to receive solution components and mix them into a mixed liquid having a predetermined characteristic, such as pH level and / or conductivity in a predetermined range. In the present example, the mixing arrangement 230 comprises a plurality of inlets 10 for receiving a respective solution component, or buffer component. The inlets may be configured to receive solution components as follows: the first inlet 11 an acidic buffer substance, the second inlet 12 a basic buffer substance, the third inlet 13 WFI, the fourth inlet 14 a salt, and the fifth inlet 15 one or more additives. Each inlet 11-15 may be connected to a respective pump 231, 232, 233, 234, 235 for driving a flow of the respective solution component to the conduit 220 to form a mixed liquid or a certain set of characteristics. Thus, one of the pumps (pump 233) may be a WFI pump whereas the other pumps (pumps 231, 232, 234, 235) may be stock solution pumps. In the present example, the pumps may be diaphragm pumps. However, other pump types, using other operation principles, are also possible.

[0064] Sensors, such as a pH sensor 342 and a conductivity sensor 344, may be arranged to measure the corresponding characteristics of the mixed liquid and generate sensor output to the controller 240.

[0065] The valve arrangement 210 is configured to receive the mixed liquid from the conduit 220 and distribute the mixed liquid to one or more of the bioprocessing stations 110, 120, 130. For this purpose, the valve arrangement 210 comprises a capture outlet 211 connected to the mixed liquid inlet 113 of the capture station 110, an NFF outlet 212 connected to the mixed liquid inlet 123 of the NFF station 120, and a polishing outlet 213 connected to the mixed liquid inlet 133 of the polishing station 130. Further, a waste outlet 214 is provided to allow the mixed liquid to be discarded, in case, e.g., any of the characteristics of the mixed liquid falls outside the acceptable range for that characteristic.

[0066] It should be noted that that figure 2 is a simplified representation of a bioprocessing system, and that any of the bioprocessing stations 110, 120, 130, 140 and the liquid supply apparatus 200 may comprise additional features and functionalities not depicted in the figure.

[0067] An exemplary operation sequence of the bioprocessing system illustrated in figure 2 will now be described with reference to the flow chart 1000 of figure 3. The illustrated operation sequence is a purification process involving chromatographic columns and should be seen as illustrating rather than limiting the scope of the inventive concepts and examples disclosed herein.

[0068] In a first process step SI 10 the liquid supply apparatus 200 equilibrates the capture column 115 of the capture station 110 by supplying a mixed liquid prepared from an acidic buffer substance, a basic buffer substance, salt, and WFI to the mixed liquid inlet 113 of the capture station 110. The mixed liquid is passed through the capture column 115 and released by the release valve 117 to the waste outlet 114. The equilibration is typically performed to establish the correct pH and ionic strength in the stationary phase, aligning the stationary phase with the conditions necessary for the specific chromatographic technique used.

[0069] Thereafter, the sample is loaded S120 into the capture column 115. The sample may be a filtrate pumped from a mixer 20 by means of a sample pump 21. The flow of the sample may be directed to the capture column 115 by means of the inlet valve 116, which may be arranged to open a flow path between the sample pump 21 and the capture column 115 and at the same time close the flow path to the mixed liquid inlet 113 to prevent a backflow towards the liquid supply apparatus 200. The sample may be provided to the capture column 115 by means of the sample pump 21 driving a flow of the sample through inlet valve 116. During the loading S120 of the capture column 115, the release valve 117 may be operated to direct the output from the capture column 115 to the waste outlet 114.

[0070] In a next step, the liquid supply apparatus 200 may be used to elute SI 30 the capture column 115 and allow the target material to be collected by the inactivation station 140. In the elution process S130, the mixed liquid forms an eluent (such as solvent or buffer) disrupting the interaction between the target material and the stationary phase of the capture column 115, allowing the target material (also referred to as an eluate) to be washed out of the column. In this step, the inlet valve 116 is operated to open the flow path between the mixed liquid inlet 113 and the capture column 115 and the release valve 117 operated to open a flow path from the outlet of the capture column 115 to the feed outlet 112 connected to the inactivation station 140.

[0071] After the elution SI 30, the capture column may be regenerated SI 40 to remove any remaining target material and impurities and restore the column 115 to its initial state. The regeneration may include the liquid supply apparatus 200 supplying the capture column 115 with a buffer that is passed to the waste outlet 114. In a separate process, which may be performed simultaneously with the regeneration step S140 or separately, a virus inactivation process SI 50 may be performed, in which the eluate is exposed to an acid that is added to a first incubation mixer 141 of the inactivation station 120. The inactivation process S150 may further include transferring the low-pH eluate to the second incubation mixer 142, where the eluate may be incubated and neutralised by a base added from a single-use container 144. After the regeneration S140 of the capture column 115, the depth filter 125 of the NFF station 120 may be equilibrated S160 by a buffer provided by the liquid supply apparatus 200. The equilibration SI 60 may be performed at the same time as at least a part of the virus inactivation process SI 50 or at a time separate from the virus inactivation process SI 50. The depth filter 125 is typically equilibrated S160 by passing a buffer through the filter to wet the filter and remove any air and impurities that might be present. The buffer may be provided as a mixed liquid from the NFF outlet 212 of the liquid supply apparatus 200 and passed on to the waste outlet 124 by the release valve 127.

[0072] The neutralised eluate may then be filtered SI 70 in a process in which it is supplied from the second incubation mixer 142 via feed inlet 121 to the depth filter 125 and further to the NFF mixer 128. During the filtration S170, the inlet valve 126 may be arranged to open the flow path for the eluate and close the flow path for the mixed liquid to prevent the eluate from forming a backflow towards the liquid supply apparatus 200. Similarly, the release valve 127 may be operated to close the flow path to the waste outlet 124 and open a flow path to the feed outlet 122.

[0073] In the present example, the liquid supply apparatus 200 is operated to equilibrate SI 80 the polishing column 130 while the eluate is being filtered S170 by the NFF station 120. The equilibration S 180 may be similar to the equilibration S 110 of the capture column 115 and may thus include supplying a buffer to the mixed liquid inlet 133 of the polishing station 130 and passing the buffer through the polishing column 115 to the waste outlet 134.

[0074] The filtration process S170, in which the eluate is filtrated by the depth filter 125, may be finished by a flushing process S190 in which the inlet valve 123 is operated to open a flow path between the liquid supply apparatus 200 and the depth filter 125 to allow a mixed liquid prepared by the liquid supply apparatus 200 to flush the filter and drive any remaining eluate in the depth filter 125 towards the NFF mixer 128.

[0075] The eluate may then be fed from the NFF mixer 128 to the feed inlet 131 of the polishing column 135 for loading S200 the polishing column 135. The loading may be assisted by the feed pump 22, which drives the feed through the inlet valve 136 to the polishing column 135. During this operation, the inlet valve 136 may be arranged to close the flow path between the mixed liquid inlet 133 and the polishing column 135 to prevent the eluate from flowing towards the liquid supply apparatus 200. During the loading S200, the release valve 137 may be operated to release the output from the polishing column 135 to the waste outlet 134. In the final step in the method 1000 of figure 3, the liquid supply apparatus 200 may be used to elute S210 the polishing column 135 and allow the target material to be collected by the mixer 138. The elution may be similar to the elution S130 of the capture column 115 described above.

[0076] Some or all of the above processing steps may be controlled by the controller 240, which hence may be configured to cause the liquid supply apparatus 200 to provide the required mixed liquid to the respective bioprocessing stations, as well as controlling the operation of one or more of the pumps 21, 22 and one or more of the valves 116, 117, 126, 127, 136, 137 to direct the flow of mixed liquid and target material through the bioprocessing system. The controller 240 may comprise circuitry configured to carry out functions of the controller, wherein the circuitry may comprise a processor, such as a central processing unit, CPU, microcontroller, or microprocessor configured to execute program code. The program code may for example be configured to carry out an evaluating function for evaluating a pH level or conductivity level based on signal output from the pH sensor 342, the conductivity sensor 344, or a sample sensor (not shown) arrange to measure a concentration of target material in the feed. The controller 240 may further comprise a memory, which may be one or more of a buffer, a flash memory, a hard drive, a removable media, a volatile memory, a non-volatile memory, a random-access memory (RAM), or another suitable device. In a typical arrangement, the memory may include a non-volatile memory for long term data storage and a volatile memory that functions as a system memory for the circuitry. The memory may exchange data with the circuitry over a data bus. Accompanying control lines and an address bus between the memory and the circuitry may be present.

[0077] The processing functions of the controller 240 may be embodied in the form of executable logic routines (e.g., line of code, software programs, etc.) that are stored on a non- transitory computer readable medium (memory) of the controller 240 and are executed by the circuitry. Furthermore, the processing functions of the controller 240 may be a stand-along software application or form a part of a software application. The described functions may be considered a method that a processing unit, e.g., the processor of the circuitry is configured to carry out. Also, while the described functions may be implemented in software, such functionality may as well be carried out via dedicated hardware or firmware, or some combination of hardware, firmware and / or software. Figure 4a is a schematic diagram of a bioprocessing system operable to perform a plurality of bioprocessing operation on a liquid flow comprising a mixed liquid carrying a sample, or target material. The system comprises a bioprocessing component 310, which may be similarly configured as any of the bioprocessing components discussed above with reference to figures 1-3. The bioprocessing component 310 may hence be a chromatography column for performing a chromatography operation, a filter device for performing a filtering operation, or a virus inactivation incubator for inactivating any virus present in the eluent.

[0078] The system further comprises a pump unit 320 for driving a flow of the mixed liquid through a tubing system 400 to the bioprocessing component 310. The mixed liquid, which for example may be a buffer solution, may be similar to the mixed liquid discussed in connection with figure 1-3 and thus used to drive the target material through the bioprocessing system. The mixed liquid may be provided from a mixed liquid supply 10, such as a storage tank or single-use container.

[0079] The pump unit 320 may be operated to drive the flow of mixed liquid through the system towards a position or junction where the sample is added to the flow in the conduit 430. The sample may be supplied from a sample supply 422, which may comprise a sample pump 446 arranged to drive a flow of the sample from a mixer 20 or single-use container 20 and add the sample to the mixed liquid to form the liquid flow that is fed to the bioprocessing component 310. The sample supply is arranged to add the sample to the conduit 430 at a portion between the pump unit 320 driving the flow of the mixed liquid and the bioprocessing component 310. By adding the sample downstream the pump unit 320, the risk for the sample contacting the pump unit 320 can be reduced and the pump unit 320 can therefore be reused between different sample batches. To further reduce the risk of contact between the pump unit 320 and the sample a protection valve 350 may be added between the sample supply point and the pump unit 320. The protection valve 350 may be operable to close the flow path to the pump unit when the sample is being pumped into the conduit 430. In some examples, the sample is added as close to the bioprocessing component 310 as possible to reduce the length of the flow path between the sample pump 466 and the bioprocessing component 310.

[0080] The tubing system 400, guiding the sample flow from the sample supply 442 to the bioprocessing component 310 and further towards the feed outlet 450 downstream the bioprocessing component 310, may be a disposable tubing system comprising one or more conduits configured to be replaced between processing operations or sample batches. The pump unit 320, on the other hand, may be reused for several bioprocessing operations or sample batches, as the pump unit 320 has not been in direct contact with the sample. By separating the pump unit 320 and sample from each other, it is possible to arrange the pump unit 320 at a location that is physically separate from the parts of the bioprocessing system that are exposed to the sample. In an example, the pump unit 320 and the bioprocessing component 310 may be arranged in a separate area of a cleanroom facility, wherein the pump unit 320 may be arranged in a less clean area of the cleanroom to save footprint in the cleaner area. An example of such a configuration is illustrated in figure 5b.

[0081] One or more sensors may be arranged to measure various characteristics of the liquids flowing through the system, such as the mixed liquid pumped by the pump unit 320, the liquid flow supplied to the bioprocessing component 310 via component inlet 422, and the output from the bioprocessing component 310 at component outlet 424. In the example shown in figure 4a, a pH sensor 342 and a conductivity sensor 344 may be arranged upstream the sample supply point, i.e., in the reusable part of the system, whereas a sample sensor, such as a UV sensor operable to measure a concentration or amount of target material in the feed discharged from the bioprocessing component 310, may be arranged downstream the bioprocessing component 310, in a disposable part of the system.

[0082] It will be appreciated that the diagram in figure 4a is a simplified version leaving out one or more components and features. For example, there may be provided additional sensors, valves, air traps, filters, and the like, which are not depicted in the present figure.

[0083] The pumps used for driving the flow through the bioprocessing system, such as the sample pump 446 and the pump unit 320 for the mixed liquid, may be of various types and depend on the flow rate and pressure requirements, as well as the specific system configuration. In some examples, a peristaltic pump may be employed, in which a flexible tube (such as the conduit 430) is compressed and released in a controlled manner to move the fluid forwards. In other examples, a diaphragm pump may be utilised, using a flexible diaphragm that moves back and forth to create a pumping action. In further examples, a piston pump is employed, in which the movement of pistons in a chamber creates a pressure driving the fluid.

[0084] The disposable part of the system 300, i.e., the tubing system 400 guiding the mixed liquid and the sample through at least parts of the bioprocessing system, will now be discussed with reference to figure 4b. The tubing system 400 may also be referred to as a flow kit and may be provided as a consumable or single-use component. The tubing system 400 may thus be configured to be used for a specific bioprocessing operation or sample batch and replaced after the bioprocessing operation or sample batch has been completed. Before a new bioprocessing operation or sample batch is initiated, the tubing system 400 may be replaced with a clean and preferably pre-sterilised one.

[0085] Figure 4b illustrates an example of such a tubing system 400. The tubing system 400 comprises a plurality of inlets 410, 444 and outlets 422, 424, 450, between which flow paths are formed by tubing of conduits arranged to guide liquids between various components and processing steps of the bioprocessing system. In the present example, the tubing system 400 comprises an inlet branch comprising a conduit 430 with a mixed liquid inlet 410 configured to be coupled to the pump unit 320 shown in figure 4a, or more specifically to the protection valve 350 protecting the pump unit 320 and the sensors 342, 344 from coming into contact with the sample. The tubing system 400 further comprises a sample inlet 440 configured to supply the sample to the flow of the mixed liquid in the conduit 430. A flow of the sample provided at the sample inlet 440 may be driven by the sample pump 446, which hence may be integrated in the disposable tubing system 400 and replaced together with the rest of the tubing system 400. The sample pump 446 may, for example, comprise a disposable pump head which may be connectable to a reusable pump body or drive unit. The flow of the sample may join the flow of the mixed liquid at a position of the conduit downstream the mixed liquid inlet 410, and thus downstream the pump unit 320 and the sensors 342, 320.

[0086] The conduit 430 may be arranged to guide the liquid flow, comprising the sample carried by the flow of mixed liquid, to a processing component inlet 422. The processing component inlet 422 is configured to be coupled to an inlet of the bioprocessing component 310 to supply the sample to the same. The tubing system 400 further comprises an outlet branch, comprising processing component outlet 424 configured to be coupled to an outlet of the bioprocessing component 310 to receive the output from the bioprocessing component 310 and guide the output towards a feed outlet 450, which may comprise a manifold with a plurality of outlets. In the present example, a bypass path 425 may be provided between the processing component inlet 422 and the bioprocessing component outlet 424 to allow the bioprocessing component to be bypassed.

[0087] Additionally, one or more sensors may be incorporated into the disposable tubing system 400. In figure 4b, a sample sensor 460, similar to the one shown in figure 4a, is arranged in the outlet branch. The individual fluid lines or conduit(s) forming the flow paths of the tubing system 400 may be flexible to facilitate handling and installation and to enable pinch valves to be formed to open and close the flow paths during operation of the bioprocessing system 300. The conduits may be formed of an elastomeric material, including one or more of silicone rubber, a thermoplastic elastomer, or a thermoplastic rubber.

[0088] As previously mentioned, the tubing system 400 may be provided in a pre-sterilised, sealed container or bag. To maintain the sterility, one or more or the inlets / outlets may be provided with a barrier of sterile filter that can be removed or broken upon installation of the tubing system 400, or a connector allowing for sterilisation (e.g., via steam) of the connection point in connection with the installation.

[0089] Figure 5a is a schematic representation of the tubing system 400 when attached to a base unit 500, or skid. The base unit may form a self-contained, modular unit that can be transported (e.g. by means of wheels 502 provided for this purpose) and integrated into a larger processing system. In the context of the present disclosure, the base unit 500 may correspond to a bioprocessing station as discussed above in connection with figures 1-3.

[0090] The base unit 500 comprises a housing with a plurality of valve actuators 508, 510, 512, 514-517 configured to releasably engage a portion of a conduit of the tubing system 400 to form a pinch valve controlling a flow through the tubing system. Each valve actuator may be arranged to cooperate with a cassette, or valve housing, defining a channel through which the conduit may pass and wherein the valve actuator can be moved relative to the cassette to reduce the cross section of the channel, thereby pinching the conduit, and causing it to close. Deactivating the valve actuator subsequently causes the conduit to resiliently return towards its initial open state and thus enable fluid flow therethrough.

[0091] The valve actuators may be individually operable by the controller 240, which may be provided in the base unit 500 or elsewhere. In some examples, the controller 240 may be distributed between several nodes, or comprise a plurality of submodules, which may be arranged in each of the valve actuators or elsewhere.

[0092] The base unit 500 may further comprise a user interface, or human machine interface (HMI) allowing an operator to interact with the bioprocessing system and control the operation thereof.

[0093] The base unit 500 may also be arranged to provide the power supply required to drive, for example, the sample pump 446. In the example shown in figure 5a, the base unit 500 and the mounted tubing system 400 form a first inlet valve 508 upstream the sample supply point, in which the sample supply 442 adds the sample to the flow of mixed liquid, and a second inlet valve 510 downstream the sample supply point. The processing component inlet 422 and the processing component outlet 424 are coupled to a processing component, in this example a chromatography column 310, and a processing component outlet 512 is formed downstream the processing component 310. Further, a bypass valve 511 is formed with the bypass path 425 extending between the processing component inlet 422 and the processing component outlet 424 to allow the processing component 310 to be bypassed. The manifold tubing, comprising a plurality of outlets 450, may be engaged by a plurality of outlet valve actuators to allow for a controlled release of the output feed to, for instance, the waste outlet or a subsequent processing station as discussed in connection with figures 1-3. In the present example, four different outlets 451- 454 are provided, each of which being controlled by a respective pinch valve 514-517.

[0094] The conduits or tubing forming the inlet branch 430 conveying the mixed liquid and the sample to the processing component 310, as well as the conduits or tubing forming the outlet branch 431 conveying the output from the processing component 310 to the feed outlet(s) 450 may be configured for single use, as discussed above. This may also include the sample pump 446.

[0095] The present configuration, in which the sample is added at a position downstream the pump unit 320, allows for the pump unit 320 to be configured for multiple use. In different words, the pump unit 320 does not need to be replaced together with the tubing system 400. Beneficially, this further allows for the pump unit 320 to be arranged at a location that is different from the location in which the rest of the bioprocessing system is arranged, or at least in which the bioprocessing component 310 or base unit 500 is arranged.

[0096] Figure 5b shows an example of such a configuration, in which the base unit 500, carrying a bioprocessing component 310, is arranged in a first area 610 and the pump unit 320 is arranged in a second area 620, different from the first area 610. The first and second areas 610, 620 may form part of a cleanroom facility designed to prevent particulate and microbial contamination of the biopharmaceutical products processed by the bioprocessing system. In the present example, the first area 610 may be maintained at a relatively high cleanliness level, or grade, such as ISO class 7, whereas the second area 620 may be maintained at a lower grade of cleanliness. The first area 610 may also be referred to as a processing area, and the second area 620 as a service area. The first area 610 and the second area 620 may be separated from each other by a wall and the mixed liquid passed through the wall by a through-connection, to which the mixed liquid inlet 410 of the tubing system 400 may be releasably coupled. Beneficially, this configuration allows for processing equipment and material supply flows to be separated. More specifically, the mixed liquid supply 10 and the pump unit 320 may be provided in the less clean service area 620 whereas the bioprocessing component 310 can be kept in the highly controlled processing area 610. Further, one or more sensors, such as the pH sensor 342 and the conductivity sensor 344, may be arranged in the service area 620.

[0097] It will be appreciated that a similar configuration may apply to the liquid supply apparatus 200 discussed above in connection with figures 1-3. In different words, the liquid supply apparatus 200, or part of the apparatus, such as the mixing arrangement 230 supplying one or more solution components to the conduit 220, may be arranged in the second area 620, whereas one or more of the plurality of bioprocessing stations 100 may be arranged in the first area 610. In some examples, the liquid supply apparatus 200 may be operable to supply a plurality of production lines, each comprising a plurality of interconnected bioprocessing stations 100. The plurality of production lines may be arranged in the same processing area 610 or in separate processing areas. In an example, a hub and spoke arrangement may be envisaged, in which the liquid supply apparatus 200 is arranged in the hub and supplies a plurality of production lines forming the spokes.

[0098] Various embodiments of the invention thus allow for efficient provision of inline conditioned fluid for various unit operations (e.g. for different operations such as filtration, chromatography etc. where effluent from one skid can be used as an input to a next skid for providing continuous downstream purification). Various feeds may also be provided in a closed loop, such that a fully automated system may further be provided. Advantageously, embodiments of the invention may also provide in-line conditioning (e.g. of buffer fluids) that require different concentrations, gradient profiles etc. for different unit operations and / or at different times. A further benefit of certain embodiments of the present invention is that a reduced stock preparation inventory is required, such that storage requirements and associated logistic complexity is reduced.

[0099] Also, beneficially, embodiments of the present invention can allow for buffer preparation to be performed in a in non-regulated area (e.g. outside of a cleanroom). This improves logistics as well as improving associated sustainability aspects (e.g. by reducing the amount of single use packaging etc. that would otherwise be required for in-cleanroom buffer production).

[0100] The above embodiments are to be understood as illustrative examples of the invention.

[0101] It is to be understood that any feature described in relation to any one embodiment may be used alone, or in combination with other features described, and may also be used in combination with one or more features of any other of the embodiments, or any combination of any other of the embodiments. Furthermore, equivalents and modifications not described above may also be employed without departing from the scope of the invention, which is defined in the accompanying claims.

Claims

CLAIMS:

1. A bioprocessing system for separating a target material of a feed from one or more impurities, the system comprising: a plurality of bioprocessing stations (100), each configured to perform a respective bioprocessing operation on the feed, the plurality of bioprocessing stations being interconnected such that an outlet (112) of a first one of the plurality of bioprocessing stations is connected to an inlet (121) of a next one of the plurality of bioprocessing stations; a liquid supply apparatus (200) comprising a valve arrangement (210), a conduit (220), a mixing arrangement (230), and a controller (240); wherein the mixing arrangement is configured to supply at least a first solution component and a second solution component to the conduit, thereby forming a mixed liquid; the valve arrangement is fluidically connected to the conduit and operable to selectively supply the mixed liquid to each of the bioprocessing stations; and the controller is configured to, for each bioprocessing station, control the operation of the mixing arrangement such that the mixed liquid comprises a predetermined set of characteristics associated with the bioprocessing operation of said bioprocessing station.

2. The system according to claim 1, wherein each of the plurality of bioprocessing stations comprises a bioprocessing component (115, 125, 135) being at least one of a chromatography column, a filter, and a mixer.

3. The system according to any of the preceding claims, wherein the target material is a biological target material.

4. The system according to any of the preceding claims, wherein the first solution component is a first buffer substance, the second solution component is a section buffer substance, and wherein the mixed liquid is a buffer liquid.

5. The system according to any of the preceding claims, wherein the liquid supply apparatus further comprises a control sensor arrangement (250) configured to output a signal indicating a characteristic of the mixed liquid, and wherein the controller is configured tocontrol the operation of the mixing arrangement based at least in part on the signal from the control sensor arrangement.

6. The system according to any of the preceding claims, wherein each of the plurality of bioprocessing stations comprises an inlet valve arrangement (116) configured to control a supply of feed and mixed liquid to the bioprocessing station.

7. The system according to any of the preceding claims, wherein each of the plurality of bioprocessing stations comprises a release valve arrangement (117) configured to control release of feed and mixed liquid from the bioprocessing station.

8. The system according to any of the preceding claims, wherein the plurality of bioprocessing stations is adapted to be arranged in processing area maintaining a first grade of cleanliness, and wherein the mixing arrangement is adapted to be arranged in a service area maintaining a second grade of cleanliness, the second grade being lower than the first grade.

9. A method (1000) for separating a target material of a feed from one or more impurities, comprising: supplying the feed to a plurality of bioprocessing stations, each configured to perform a respective bioprocessing operation on the feed, the plurality of bioprocessing stations being interconnected such that an outlet of a first one of the plurality of bioprocessing stations is connected to an inlet of a next one of the plurality of bioprocessing stations; mixing, in a mixing arrangement, at least a first solution component and a second solution component to form a mixed liquid; selectively supplying the mixed liquid to each of the plurality of bioprocessing stations; and for each of the plurality of bioprocessing stations: operating the mixing arrangement to provide the mixed liquid with a predetermined set of characteristics associated with the bioprocessing operation performed by said bioprocessing station.

10. The method (1000) according to claim 9, wherein the bioprocessing operation in at least one of the plurality of bioprocessing stations comprises an equilibration phase, a sample loading phase, an elution phase, and a regeneration phase.

11. The method (1000) according to claim 10, comprising: operating an inlet valve arrangement to supply the mixed liquid to the bioprocessing station during the equilibration phase, the elution phase, and the regeneration phase, and to supply the sample to the bioprocessing station during the sample loading phase.

12. The method (1000) according to claim 10 or 11, comprising: operating a release valve arrangement to release an output from the bioprocessing station to a waste outlet during the equilibration phase, the sample loading phase, and the regeneration phase, and to release the output to the next one of the plurality of bioprocessing stations during the elution phase.

13. The method (1000) according to any of claims 9-12, wherein the plurality of bioprocessing stations are arranged in a processing area of a cleanroom facility and the mixing arrangement is arranged in a service area for supply of material to the plurality of bioprocessing stations, the service area being separated from the processing area by a wall.

14. A bioprocessing system (300) operable to perform a plurality of bioprocessing operations on a liquid flow comprising a mixed liquid carrying a sample, the bioprocessing system comprising: a bioprocessing component (310) operable to perform at least one of the bioprocessing operations on the liquid flow; a pump unit (320) operable to drive a flow of the mixed liquid through a tubing system (400) to the bioprocessing component; and a sample supply (442) operable to add the sample to the flow of the mixed liquid at a position between the pump unit and the bioprocessing component, thereby forming the liquid flow; wherein the tubing system is a disposable tubing system configured to be replaced between each of the plurality of bioprocessing operations; andwherein the pump unit is a reusable pump unit operable to be reused for each of the plurality of bioprocessing operations.

15. The bioprocessing system according to claim 14, further comprising a base unit (500) operable to releasably engage with the tubing system.

16. The bioprocessing system according to claim 15, wherein the base unit comprises a valve actuator (510) operable to releasably engage a conduit of the tubing system to form a pinch valve controlling the flow of the mixed liquid through the tubing system.

17. The bioprocessing system according to any of claims 14-16, further comprising a sensor (342, 344) arranged upstream of the position in which the sample is added to the flow of the mixed liquid, the sensor being at least one of a pH sensor and a conductivity sensor.

18. The bioprocessing system according to any of claims 14-17, further comprising a sample pump (446) operable to supply the sample to the flow of the mixed liquid.

19. The bioprocessing system according to any of claims 14-18, further comprising a protection valve (350) operable to prevent the sample from reaching the pump unit.

20. The bioprocessing system according to any of claims 14-19, wherein the bioprocessing component is adapted to be arranged in a processing area maintaining a first grade of cleanliness, and wherein the pump unit is adapted to be arranged in a service area maintaining a second grade of cleanliness, the second grade being lower than the first grade.

21. The bioprocessing system according to claim 20 when depending on claim 17, wherein the sensor is adapted to be arranged in the service area.

22. The bioprocessing system according to any of claims 14-21, wherein the bioprocessing component is at least one of: a filter, a chromatography column, and a polishing membrane.

23. A tubing system (400) for a bioprocessing system operable to perform a plurality of bioprocessing operations on a liquid flow comprising a mixed liquid carrying a sample, the tubing system comprising: a mixed liquid inlet ( 10) configured to be coupled a pump unit of the bioprocessing system; a processing component inlet (422) configured to be coupled to a bioprocessing component of the bioprocessing system; a conduit (430) configured to convey a flow of the mixed liquid from the pump unit to the bioprocessing component; and a sample inlet (440) configured to supply the sample to the flow of the mixed liquid, the sample inlet being arranged between the mixed liquid inlet and the processing component inlet; wherein the tubing system is a disposable tubing system configured to be replaced between each of the plurality of bioprocessing operations.

24. The tubing system according to claim 23, further comprising a sterile connector arranged at each of the mixed liquid inlet, the processing component inlet, and the sample inlet to maintain a sterility of the tubing system prior to use.

25. The tubing system according to claim 23 or 24, configured to be removably attached to a base unit comprising a valve actuator.

26. The tubing system according to claim 25, wherein the conduit is adapted to be releasably engage with the valve actuator to form a pinch valve controlling the flow of the mixed liquid through the tubing system.

27. The tubing system according to any of claims 23-26, wherein the conduit is formed of an elastomeric material including one or more of: silicone rubber, a thermoplastic elastomer, and / or a thermoplastic rubber.

28. The tubing system according to any of claims 23-27, further comprising a sensor (460) operable to generate a signal indicating a concentration of the sample in the liquid flow.

29. The tubing system according to any of claims 23-28, further comprising a protection valve (350) operable to prevent the sample from reaching the pump unit.

30. A method for reconfiguring a bioprocessing system operable to perform a plurality of bioprocessing operations on a liquid flow comprising a mixed liquid carrying a sample, the bioprocessing system comprising: a bioprocessing component operable to perform at least one of the bioprocessing operations on the liquid flow; a pump unit operable to drive a flow of the mixed liquid to the bioprocessing component; and a sample supply operable to add the same to the flow of the mixed liquid, thereby forming the liquid flow; wherein the method comprises, between two consecutive bioprocessing operations of the plurality of bioprocessing operations: disconnecting a first tubing system from the pump unit, the bioprocessing component, and the sample supply, and connecting a second tubing system to the pump unit, the bioprocessing component, and the sample supply; wherein each of the first and second tubing systems is operable to convey the flow of the mixed liquid from the pump unit to the bioprocessing component.

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