Batch Chromatography Package

Abstract

A method for separating at least one target compound from a feed solution is provided. The method includes filling a bioprocess package with a chromatography resin. The bioprocess package includes a 2D flexible container having an interior compartment, a height with an upper half and a lower half, an inlet and an outlet disposed in the same half of the 2D flexible container, and a channel-forming mechanism configured to maintain a fluid flow path that fluidly connects the interior compartment of the flexible container with the outlet. The method further includes flowing a feed solution through the bioprocess package to contact the chromatography resin such that substantially all of the at least one target compound binds to the chromatography resin; washing the chromatography resin in the bioprocess package; and eluting the chromatography resin.

Description

Related Applications

[0001] This application claims the benefit of priority under 35 U.S.C. § 120 to U.S. Provisional Application No. 62 / 640,190, filed March 8, 2018, and U.S. Provisional Application No. 62 / 592,983, filed November 30, 2017, the contents of which are hereby incorporated by reference in their entireties. [Technical Field]

[0002] The present disclosure relates generally to bioprocessing bags for batch chromatography and systems using the same. In particular, the present disclosure relates to bioprocessing bags for batch chromatography having channel-forming features that facilitate the removal of fluids and / or other components from an internal compartment of the bag. [Background technology]

[0003] For example, the production of new drugs featuring monoclonal antibodies and other proteins has grown significantly and sustainably. This growth is due to the expansion of drug pipelines and the optimization of more efficient cell line and bioreactor development. Downstream purification, which often involves chromatography, is the portion of the drug production process that consumes the most significant amount of invested time and resources. Chromatography is the process of separating the product from contaminating species and is a critical step in drug production and other bioprocessing applications. However, column chromatography processes have seen little improvement. In particular, this process has not been improved due to improvements in upstream technologies that can process larger volumes over longer periods of time. While the results can be considered advantageous for some reasons, the improvements also generally lead to the production of more impurities in bioprocessing systems that could benefit from downstream chromatography methods and systems that can efficiently perform separations of larger volumes. Furthermore, conventional chromatography methods and systems have physical limitations that limit the ability to scale these methods and systems. The largest chromatography columns currently available on the market can accommodate a fraction of the volume of a single bioreactor (e.g., 10 g / L (10 g / L)). 3 cm 3 It would require multiple chromatography cycles to achieve isolation of only the product )), which can take up to 24 hours and pose a significant bottleneck to the overall drug production process.

[0004] Bags containing sterile fluids are used in the bioprocessing industry to compound, store, transfer, and transport fluids while maintaining sterile conditions. Some bag characteristics that preserve the quality of the product contained within include biocompatibility with the product, sterility, and apyrogenicity. These bags are generally discarded after use and are recognized as an efficient means for preparing and storing sterile fluids. These disposable bioprocessing bags are generally flexible and made from compatible plastics that are sterilized by gamma radiation. These bags can be used for any bioprocessing application, including, but not limited to, compounding, filling, storage, and transport of final products, refrigerated storage or deep-freezing of pharmaceuticals, and sampling and analytical purposes. These bags can also provide an environment for cell culture. Additionally, these bags can be used for biological fluids, such as serum, buffers, and ultrapure water, as well as for growing cell cultures to obtain valuable biopharmaceutical compounds produced by the cells. For chromatography processes, disposable products are beginning to be used more frequently because they are labor-saving and generally do not require cleaning. However, disposable products continue to adhere to traditional column methodology and system design mechanisms. Summary of the Invention

[0005] According to an embodiment of the present disclosure, a method for separating at least one target compound from a feed solution is provided. The method includes filling a bioprocess package with a chromatography resin. The bioprocess package includes a 2D flexible container having an interior compartment, a height with an upper half and a lower half, an inlet and an outlet located in the same half of the 2D flexible container, and a channel-forming feature within the interior compartment of the container configured to maintain a fluid flow path fluidically connecting the interior compartment of the flexible container with the outlet. The method further includes flowing a feed solution through the bioprocess package to contact the chromatography resin such that substantially all of the at least one target compound binds to the chromatography resin; washing the chromatography resin in the bioprocess package; and eluting the chromatography resin such that substantially all of the at least one target compound is released from the chromatography resin.

[0006] It is to be understood that both the foregoing general description and the following detailed description are merely exemplary and are intended to provide an overview or framework for understanding the nature and characteristics of the claims. The accompanying drawings are enclosed to provide a further understanding, and are incorporated into and constitute a part of this specification. The drawings illustrate one or more embodiments, and together with the description, serve to explain the principles and operation of the various embodiments. [Brief explanation of the drawings]

[0007] The present disclosure will be more clearly understood from the following description and the accompanying drawings, given purely by way of non-limiting example. [Figure 1] FIG. 1 is a diagram of an exemplary bioprocess bag having a channel forming feature according to an embodiment of the present disclosure. [Figure 2A] FIG. 1 is a schematic diagram of an exemplary bioprocess bag having a channel forming feature according to an embodiment of the present disclosure. [Figure 2B] FIG. 2B is a schematic diagram showing a side view of the bioprocess bag with the channel forming feature of FIG. 2A. [Figure 2C] FIG. 2C is an enlarged and exaggerated schematic diagram showing a top view of the bioprocess bag with the channel forming features of FIG. 2B. [Figure 3A] FIG. 1 is a schematic diagram of an exemplary bioprocess bag having a channel forming feature according to an embodiment of the present disclosure. [Figure 3B] FIG. 1 is a schematic diagram of a port fitting having a channel forming feature attached thereto according to an embodiment of the present disclosure. [Figure 3C] 3C is a cross-sectional view of the port fitting of FIG. 3B taken along line 1-1' of FIG. 3B. [Figure 4A] FIG. 1 is a schematic diagram of a bioprocess bag having a channel forming feature according to an embodiment of the present disclosure. [Figure 4B] FIG. 4B is a schematic diagram showing a side view of the bioprocess bag with the channel forming feature of FIG. [Figure 5] 1A and 1B are diagrams of an exemplary port attachment according to an embodiment of the present disclosure. [Figure 6] 1 is a cross-sectional view of an exemplary port fitting according to an embodiment of the present disclosure. [Figure 7] 10A-10C are diagrams of exemplary channel forming mechanism extenders according to embodiments of the present disclosure. [Figure 8] 10A-10C are diagrams of exemplary channel forming mechanism extenders according to embodiments of the present disclosure. [Figure 9] 10A-10C are diagrams of exemplary channel forming mechanism extenders according to embodiments of the present disclosure. [Figure 10] 1 is a flowchart illustrating a method according to an embodiment of the present disclosure. [Figure 11A] FIG. 1 is a schematic diagram of a bioprocess bag having a channel forming feature according to an embodiment of the present disclosure. [Figure 11B] FIG. 11B is a schematic diagram showing a side view of the bioprocess bag with the channel forming feature of FIG. [Figure 12] FIG. 1 is a diagram of an exemplary face port consistent with an embodiment of the present disclosure. DETAILED DESCRIPTION OF THE INVENTION

[0008] Reference will now be made in detail to the present embodiment(s), example(s), as illustrated in the accompanying drawings. Wherever possible, the same reference numbers will be used throughout the drawings to refer to the same or like parts.

[0009] The singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. The endpoints of all ranges describing the same property are independently combinable and inclusive of the recited endpoints. All references are incorporated herein by reference.

[0010] As used herein, the words "have," "having," "include," "including," "comprise," "comprising," and the like are used in their open-ended sense and generally mean "including, but not limited to."

[0011] All scientific and technical terms used herein have meanings commonly used in the art unless otherwise specified. The definitions provided herein are intended to facilitate understanding of certain terms used frequently herein and are not meant to limit the scope of the present disclosure.

[0012] The present disclosure will be described below generally and then in detail based on several exemplary embodiments. Features shown in combination with each other in individual exemplary embodiments need not all be realized. In particular, individual features may be omitted or combined in some other way with other features shown in the same exemplary embodiment or in other exemplary embodiments.

[0013] Embodiments of the present disclosure relate to bioprocess bags. The bioprocess bags described herein are 2D bags formed from flexible materials. As used herein, the term "2D bag" refers to a flat, rectangular, "pillow-shaped" bag formed by seaming two flexible sheets together. Bioprocess bags according to embodiments of the present disclosure are formed from disposable materials and are disposable after a single use, thereby eliminating the cleaning / sterilization operations and maintenance associated with traditional cell culture vessels. Advantageously, the bioprocess bags described herein allow for the aseptic transfer of a feed solution from a cell culture vessel, for example, from a bioreactor, to the bag, where batch chromatography can be performed within a single vessel. The bioprocess bags described herein allow these operations to occur without exposing the desired product to the ambient atmosphere.

[0014] FIG. 1 illustrates a bioprocess bag according to an embodiment of the present disclosure. As shown, the bioprocess bag 100, 1100 includes at least two sheets 102, 104 formed from a film or laminate. The sheets 102, 104 are sealed (e.g., by welding or adhesive) along their edges to form a pillow-shaped bag with an internal compartment for receiving fluids. The bioprocess bag 100, 1100 preferably creates a closed system for use at all stages of processing fluids and / or other components. FIG. 1 illustrates an exemplary configuration of a bioprocess bag formed from two sheets 102, 104 that are longer than their width and that, when attached along their edges, form the bioprocess bag 100, 1100 having two sides, a top and a bottom, where the two sides are longer than the width of the top and bottom. It should be understood that this is merely an exemplary configuration, and the bioprocess bag described herein can have a top, bottom, and two sides of equal length. The bioprocess bag 100, 1100 is described herein as having two sides, a top and a bottom. However, it should be understood that terms such as "top," "bottom," and "side" are used herein for descriptive purposes only and do not necessarily represent permanent relative positions. It should be understood that the terms used herein are interchangeable under appropriate circumstances, such that embodiments of the present disclosure are operable in orientations other than those illustrated or described herein.

[0015] Each sheet 102, 104 of the bioprocess bag 100, 1100 may be formed from one or more of the same or different materials. These materials are traditionally associated with disposable products for bioprocessing applications. Any or all of the sheets 102, 104 of the bioprocess bag 100, 1100 may be formed from a film or laminate including at least one plastic material from the following group: polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC), polyethylene terephthalate (PET), polystyrene (PS), polycarbonate (PC), polymethylpentene (PMP), polyetheretherketone (PEEK), polytetrafluoroethylene (PTFE), polyfluoroalkoxy (PFA), polychlorotrifluoroethylene (PCTFE), ethylene vinyl acetate (EVA), and derivatives thereof.

[0016] It should be understood that the dimensions of the bioprocess bag 100, 1100, including both relative and absolute dimensions, can vary. For example, the bag may contain approximately 1.0 mL (1.0 cm 3 ), or approximately 5.0 mL (5.0 cm 3 ), or approximately 10 mL (10 cm 3 ), or approximately 25 mL (25 cm 3 ), or approximately 50 mL (50 cm 3 ), or approximately 100 mL (100 cm 3 ), or approximately 250 mL (250 cm 3 ), or approximately 500 mL (500 cm 3 ), or approximately 1.0 L (1.0 x 10 3 cm 3 ), or 5.0L (5.0 x 10 3 cm 3 ), or approximately 10L (10 x 10 3 cm 3 ), or approximately 50L (50 x 10 3 cm 3 ), or approximately 100L (100 x 10 3 cm 3 ), or approximately 150L (150 x 10 3 cm 3), or even about 200L (200 x 10 3 cm 3 ), and all volumes in between.

[0017] The total thickness of the film or laminate can be selected based on, for example, the desired gas permeability of the bioprocess bag 100, 1100, or based on the desired stiffness or flexibility of the bag 100, 1100. For example, the thickness of the sheets 102, 104 can be from about 0.002 inches (0.00508 centimeters) to about 1.5 inches (3.81 centimeters). As described herein, the thicknesses of the sheets 102 and 104 can be the same or different.

[0018] The bioprocess bag 100, 1100 may be sealed and have one or more openings for introducing or withdrawing fluids and / or other components. If the bioprocess bag 100, 1100 includes one or more openings, the one or more openings may include a seal that, in a first configuration, exposes the one or more openings to sterile fluid communication between an external container and an internal compartment of the bag through the opening. In a second configuration, the seal closes the one or more openings, preventing or reducing fluid communication between the exterior of the bag and an internal compartment of the bag through the opening. The seal can take any desired shape, including, but not limited to, a clamp, tape, a cap, a tubing section with welded ends, a zipper, a sliding zipper, an interlocking or coupling structure, a sterile connector, etc.

[0019] The bioprocess bag 100, 1100 described herein includes at least one fitting including an internal flow path that allows fluids and / or other components to flow into or out of an internal compartment of the bioprocess bag 100, 1100. With further reference to FIG. 1 , the at least one fitting may be at least one connector 140 including an internal flow path that allows fluids and / or other components to flow into or out of an internal compartment of the bioprocess bag 100. The at least one connector 140 includes a proximal end and a distal end and extends through an opening formed in a portion of the sealed edge of the bioprocess bag 100. The proximal end of the at least one connector 140 may extend through the opening into an internal compartment of the bioprocess bag 100. Alternatively, rather than extending into the internal compartment of the bioprocess bag 100, the proximal end of the at least one connector 140 may be disposed within the opening to allow fluids and / or other components to flow into or out of the internal compartment of the bioprocess bag 100. At least a portion of the film or laminate of sheets 102, 104 is heat sealed or otherwise adhered around at least one connector 140 so that the bioprocess bag 100 is sealed.

[0020] 11A and 11B, the at least one connector may be at least one outward-facing face port 1140 that includes an internal flow path that allows fluids and / or other components to flow into or out of an internal compartment of the bioprocess bag 1100. The outward-facing face port 1140 may be formed in a face of at least one of the sheets 102, 104. As shown in FIG. 12, the at least one face port 1140 may include a base flange 1150 having a top surface 1152 and a bottom surface 1154. At least a portion of the film or laminate of one of the sheets 102 and 104 is welded, heat sealed, or otherwise adhered to the base flange 1150 of the at least one face port 1140 such that the bioprocess bag 1100 is sealed. The at least one face port 1140 further includes an extension 1144 that extends a predetermined length from the base flange 1150 and is configured to engage the open end of a length of tubing. The extension 1144 may include a coupler, such as a barb 1160, at one end to facilitate engagement with the open end of the tubing. According to embodiments of the present disclosure, the at least one face port 1140 is configured such that the extension 1144 extends outside the bioprocess bag 1100 and does not extend into the interior compartment of the bioprocess bag 1100. One of sheets 102 and 104 may be welded, heat sealed, or otherwise adhered to the top surface 1152 of the base flange 1150. Alternatively, one of sheets 102 and 104 may be welded, heat sealed, or otherwise adhered to the bottom surface 1154 of the base flange 1150. As used herein, the term "face port" refers to a port located on the face of at least one of sheets 102 and 104, but not on an edge or seam of the bioprocess bag 100, 1100.As used herein, the term "outward-facing face port" refers to a face port having an extension that extends from the sheet to the outside of the bioprocess bag and does not extend into the interior compartment of the bioprocess bag. Conversely, as used herein, the term "inward-facing face port" refers to a face port having an extension that extends from the sheet into the interior compartment of the bioprocess bag.

[0021] The at least one connector 140 or the at least one face port 1140 can be a relatively rigid plastic component formed from, for example, but not limited to, high density polypropylene (HDPP), polypropylene, high density polyethylene (HDPE), polyethylene, EVA, LDPE, and LLDPE. Optionally, the at least one connector 140 can be a flexible plastic tubing. If the at least one connector 140 is a relatively rigid plastic component, the distal end of the at least one connector 140 is configured to engage an open end of a length of tubing that places the at least one connector 140 in sterile fluid communication with another length of tubing (i.e., through a sterile connector) or with a fitting of an external container. Similarly, if the at least one face port 1140 is a relatively rigid plastic component, the extension 1144 is configured to engage the open end of a length of tubing that places the at least one face port 1140 in sterile fluid communication with another length of tubing (i.e., through a sterile connector) or a fitting of an external container. If the at least one connector 140 is a flexible plastic tubing, the at least one connector 140 may be in sterile fluid communication with another length of tubing (i.e., through a sterile connector) or a fitting of an external container. The seals described above may interact with or be connected to the at least one connector 140, the extension 1144, and / or the other length of tubing to selectively allow or prevent fluid communication between the interior compartment of the bag 100, 1100 and the external container.

[0022] The bioprocess bag 100 may include multiple connectors 140, such as connectors 140a, 140b, and 140c shown in FIG. 1. The multiple connectors 140 may have equal dimensions, or the dimensions of each of the multiple connectors 140 may differ. It is also contemplated that at least two of the multiple connectors 140 may have equal dimensions, with at least one of the multiple connectors 140 having dimensions that differ from at least two of the multiple connectors 140. If the at least one connector 140 is a relatively rigid plastic connector, the at least one connector 140 may include a coupler configured to hold the at least one connector 140 within the bioprocess bag 100. The coupler may be a shaped portion extending from the outer wall of the at least one connector 140, around which a portion of the film or laminate of the sheets 102, 104 may be heat-sealed. The coupler may be, for example, a barb, a plastic ring, or a plastic flange. The coupler may be integrally formed with at least one connector 140 or may be separately formed and attached to at least one connector 140. When the bioprocess bag 100 includes multiple connectors 140a, 140b, 140c, where the first of the connectors 140 is an inlet and the second of the connectors 140 is an outlet, the inlet and outlet are located on the same side of the bioprocess bag 100 (i.e., the top of the bag). Optionally, a bioprocess bag 100 having more than two connectors 140 may include any number of connectors 140 located on any side of the bioprocess bag 100, so long as two of the connectors 140 are located on the same side of the bag, and the first of the two connectors 140 is an inlet and the second of the two connectors 140 is an outlet. Referring again to FIG. 1 as an example, connector 140a may be the inlet and connector 140c may be the outlet.

[0023] The bioprocess bag 1100 may include multiple face ports 1140, such as face ports 1140a, 1140b, and 1140c shown in Figures 11A and 11B. The dimensions of the multiple face ports 1140 may be equal, or the dimensions of each of the multiple face ports 1140 may be different. It is also contemplated that the dimensions of at least two of the multiple face ports 1140 may be equal and at least one other of the multiple face ports 1140 may be different from the dimensions of at least two of the multiple face ports 1140. When the bioprocess bag 1100 includes multiple face ports 1140a, 1140b, 1140c, and the first of the face ports 1140 is an inlet and the second of the face ports 1140 is an outlet, the inlet and the outlet are located in the same half of the height of the bioprocess bag 1100 (i.e., the upper half of the sheets 102, 104 of the bag). Optionally, a bioprocess bag 1100 having more than two face ports 1140 may include any number of face ports 1140 located on any side of the bioprocess bag 1100, so long as two of the face ports 1140 are located on the same side of the bag, the first of the two face ports 1140 being an inlet, and the second of the two face ports 1140 being an outlet. Referring again to Figures 11A and 11B as an example, face port 1140a may be an inlet and face port 1140b may be an outlet.

[0024] According to embodiments of the present disclosure, the at least one connector may be a port fitting 40, such as the port fitting 40 shown in FIG. 5, having at least one port 42 that allows fluids and / or other components to flow into or out of an internal compartment of the bioprocess bag 100. As shown in FIG. 6, the at least one port 42 is in fluid communication with an internal passage of an extension 44 that extends a predetermined length from the opening of the at least one port 42 and is configured to engage with the open end of a length of tubing. The extension 44 may include a coupler, such as a barb, at one end to facilitate engagement with the open end of the tubing. The port fitting 40 may include multiple ports 42. The dimensions of the multiple ports 42 may be equal for each of the multiple ports 42, or the dimensions of each of the multiple ports 42 may be different. It is also contemplated that the dimensions of at least two of the multiple ports 42 may be equal and at least one of the multiple ports 42 may be different from the dimensions of at least two of the multiple ports 42. According to embodiments of the present disclosure, the port fitting 40 may be any shape. The exemplary port fitting 40 shown in the figures is a boat-shaped port fitting, although the port fittings 42 disclosed herein are not limited thereto. The port fitting 40 may be a plastic port fitting formed from, for example, but not limited to, high density polypropylene (HDPP), polypropylene, high density polyethylene (HDPE), polyethylene, EVA, LDPE, and LLDPE.

[0025] A connection is formed between the polymer layer of the film or laminate of sheets 102, 104 and the port fitting 40, forming a hermetic seal between the bag 100 and the port fitting 40. As shown in FIG. 6, the port fitting 40 includes an exterior surface 54 and an interior surface 52. The connection between the bioprocess bag 100 and the port fitting 40 may be along either the exterior surface 54 or the interior surface 52. The connection may be formed by welding or another type of attachment such that a fluid-tight seal is formed between the port fitting 40 and the bioprocess bag 100, except for at least one port 42.

[0026] According to embodiments of the present disclosure, the bioprocess bag 100, 1100 includes a channel-forming feature. A problem encountered when dispensing the contents of a flexible bag is that as the bag contracts in volume, portions of the bag's sheets may collapse and contact each other, forming blocked pockets. The channel-forming feature described herein prevents the sheets 102, 104 of the bioprocess bag 100, 1100 from blocking portions of the bag 100, 1100 and / or blocking fluids and / or other components in the bag 100, 1100 from reaching the outlet. The channel-forming feature prevents the bag 100, 1100 from closing on itself, thus creating a fluid flow path for the contents of the bag 100, 1100 to reach the outlet.

[0027] 2A-2C, the channel-forming features described herein may be a solid extruded plastic component 120 extending from a first end 171 to a second end 172, with the second end 172 disposed within an interior compartment of the bioprocess bag 100. The first end 171 of the solid extruded plastic component 120 may be welded to a seam of the bioprocess bag 100, for example, a seam at the top of the bioprocess bag 100. Alternatively, the first end 171 of the solid extruded plastic component 120 may be disposed within one of the plurality of connectors 140. Similarly, if at least one fitting is a port fitting 40 described herein, the first end 171 of the solid extruded plastic component 120 may be disposed within one of the plurality of ports 42. The solid extruded plastic component 120 extends into the interior compartment of the bioprocess bag 100 a distance sufficient to prevent the sheets 102, 104 of the bioprocess bag 100 from blocking a portion of the bag 100 and / or blocking fluids and / or other components in the bag 100 from reaching the outlet. According to embodiments of the present disclosure, the solid extruded plastic component 120 may have a length that spans a distance of at least about half the distance between the top of the bioprocess bag 100 and the bottom of the bioprocess bag 100. That is, the solid extruded plastic component 120 may have a length that is at least about half the length of the sheets 102, 104 of the bioprocess bag 100, but preferably less than the entire length of the sheets 102, 104 of the bioprocess bag 100. For example, if the length of the sheets 102, 104 is represented by "L," the solid extruded plastic component 120 may have a length of about 0.5L to about 0.95L, or about 0.5L to about 0.85L, or even about 0.5L to about 0.75L. The solid extruded plastic component 120 may have any cross-sectional shape, such as circular, square, or rectangular. The solid extruded plastic component 120 may also have a shape that advantageously forms additional channels through which fluid may flow. For example, the solid extruded plastic component 120 may have a star-shaped cross-section.

[0028] As shown in Figures 3A-3C, the channel-forming feature described herein may be a tubular plastic component 122 (e.g., a section of tubing) extending from a first end 173 to a second end 174, with the second end 174 disposed within an interior compartment of the bioprocess bag 100. The first end 173 of the tubular plastic component 122 may be welded to a seam of the bioprocess bag 100, for example, to a seam at the top of the bioprocess bag 100. Alternatively, as shown in Figure 3A, the first end 173 of the tubular plastic component 122 may be attached to or disposed within one of a plurality of connectors 140. Similarly, as shown in Figures 3B and 3C, if at least one connector is a port fitting 40 described herein, the first end 173 of the tubular plastic component may be attached to or disposed within one of a plurality of ports 42. This arrangement also allows the channel-forming mechanism to form a conduit that cannot be closed by applying pressure to the sheets 102, 104 when the bioprocess bag 100 is collapsed. The second end 174 of the tubular plastic component 122 may be closed-ended or may include a plug inserted into the end of the tubular plastic component 122 to isolate the interior of the tubular plastic component 122 from the contents of the interior compartment of the bioprocess bag 100. The tubular plastic component 122 extends into the interior compartment of the bioprocess bag 100 a sufficient distance to prevent the sheets 102, 104 of the bioprocess bag 100 from blocking a portion of the bag 100 and / or blocking fluids and / or other components in the bag 100 from reaching the outlet. According to embodiments of the present disclosure, the tubular plastic component 122 may have a length that spans at least about half the distance between the top of the bioprocess bag 100 and the bottom of the bioprocess bag 100. That is, the tubular plastic component 122 may have a length that is at least about half the length of the sheets 102, 104 of the bioprocess bag 100, but preferably less than the entire length of the sheets 102, 104 of the bioprocess bag 100.For example, if the length of the sheets 102, 104 is represented by "L", the tubular plastic component 122 may have a length of from about 0.5L to about 0.95L, or from about 0.5L to about 0.85L, or even from about 0.5L to about 0.75L.

[0029] As shown in Figures 4A and 4B, the channel-forming features described herein may be raised portions 124 extending from the inner surface of at least one of sheets 102 and 104 into the interior compartment of the bioprocess bag 100. The raised portions 124 may also be textured portions of the inner surface of at least one of sheets 102 and 104. As used herein, the term "textured" refers to surface deformation (as opposed to a flat, untextured sheet) and multiple surface areas or planes created by uniaxial or biaxial folding, molding, etc., which are intentionally imparted to the surface rather than texture inherently present on the surface simply due to the surface's natural topography, surface contamination, etc. Alternatively, the raised portions 124 may be a plastic component attached to the inner surface of sheets 102, 104 using an adhesive or by heat sealing that is more rigid than the film or laminate of sheets 102, 104. Such plastic components may be formed from, for example, but not limited to, high density polypropylene (HDPP), polypropylene, high density polyethylene (HDPE), polyethylene, EVA, LDPE, and LLDPE. While these materials have some inherent flexibility when used to form relatively thin components or when a moderate amount of bending force is applied thereto, the raised portions 124 are distinguished from flexible portions of the bioprocess bag 100 in that the raised portions 124 generally maintain their shape when force is applied to dispense the contents of the bioprocess bag 100.

[0030] As shown in Figures 4A and 4B, the raised portion 124 may extend along any portion of the inner surface of at least one of the sheets 102 and 104 a distance sufficient to prevent the sheets 102, 104 of the bioprocess bag 100 from blocking a portion of the bag 100 and / or blocking fluids and / or other components in the bag 100 from reaching the outlet. The raised portion 124 shown in Figures 4A and 4B extends from the first end 175 to the second end 176 along the inner surface of at least one of the sheets 102 and 104, approximately from the top of the bioprocess bag 100 to at least about half the distance between the top and bottom of the bioprocess bag 100. The raised portion 124 shown in Figures 4A and 4B extends from approximately the top of the bioprocess bag 100 along the inner surface of at least one of the sheets 102 and 104 and is substantially linear. However, the raised portions 124 are not so limited. The raised portions 124 described herein may have any shape or follow any path extending from approximately the top of the bioprocess bag 100 along the inner surface of at least one of the sheets 102 and 104. For example, the raised portions 124 may extend from approximately the top of the bioprocess bag 100 in a curved or circuitous path. Furthermore, while the bioprocess bag 100 shown in FIGS. 4A and 4B includes one raised portion 124, the bioprocess bag 100 described herein may include any number of multiple raised portions 124 having any dimensions. Also, by way of non-limiting example, the inner surface of at least one of the sheets 102 and 104 may include multiple individual and distinct raised portions 124 of the same or different dimensions that form a pattern on the inner surface of at least one of the sheets 102 and 104. Such a pattern may generally extend from approximately the top of the bioprocess bag 100.

[0031] As shown in Figures 11A and 11B, the channel-forming feature described herein may be a tubular plastic component 1120 (e.g., a section of tubing) extending from a first end 1171 to a second end 1172. The bioprocess bag 1100 may include multiple inward-facing face ports 1180, such as face ports 1180a and 1180b shown in Figures 11A and 11B. Figure 11B illustrates the bioprocess bag 1100 without the tubular plastic component 1120 to more clearly show the inward-facing face ports 1180. The inward-facing face ports 1180 have all the same characteristics as the outward-facing face ports 1140, for example, as shown in Figure 12. In contrast to the outward-facing face port 1140, the inward-facing face port 1180 forms an extension 1144 into the interior compartment of the bioprocess bag 1100 but does not allow fluids and / or other components to flow into or out of the interior compartment of the bioprocess bag 1100. Optionally, one of sheets 102 and 104 may be welded, heat sealed, or otherwise adhered to the bottom surface 1154 of the base flange 1150 such that the interior flow path of the face port 1180 is closed to the outside of the bioprocess bag 1100. 11A illustrates a bioprocess bag 1100 having a tubular plastic component 1120, where a first end 1171 of the tubular plastic component 1120 may be attached to or disposed within the extension 1144 of one of the face ports 1180a and a second end 1172 of the tubular plastic component 1120 may be attached to or disposed within the extension 1144 of another of the face ports 1180b, as shown. Optionally, the first end 1171 of the tubular plastic component 1120 may be welded or sealed to the extension 1144 of one of the face ports 1180 and the second end 1172 of the tubular plastic component 1120 may be welded or sealed to the extension 1144 of the other of the face ports 1180.

[0032] 11A and 11B, at least two of the outward-facing face ports 1140 are positioned between the inward-facing face ports 1180. In FIG. 11A, the outward-facing face ports 1140a, 1140b are positioned substantially in line with the inward-facing face ports 1180a, 1180b, although it should be understood that this configuration is not required. The outward-facing face ports 1140a, 1140b may be positioned anywhere along the height of the bioprocess bag 1100 between the face ports 1180a, 1180b, as long as the channel-forming mechanism can form a conduit that cannot be closed by application of pressure to the sheets 102, 104 when the bioprocess bag 1100 collapses. The distance between the face ports 1180a and 1180b is sufficient to prevent the sheets 102, 104 of the bioprocess bag 1100 from blocking a portion of the bag 1100 and / or blocking fluids and / or other components in the bag 1100 from reaching the outlet. According to embodiments of the present disclosure, the distance between the face ports 1180a and 1180b may be at least about half the height of the bioprocess bag 1100. That is, the distance between the face ports 1180a and 1180b may be at least about half the length of the sheets 102, 104 of the bioprocess bag 1100, but preferably less than the full length of the sheets 102, 104 of the bioprocess bag 1100. For example, if the length of seats 102, 104 is represented by "L", the distance between face port 1180a and face port 1180b may be from about 0.5L to about 0.95L, or from about 0.5L to about 0.85L, or even from about 0.5L to about 0.75L.

[0033] 7-9 illustrate exemplary channel forming feature extenders configured to support or otherwise couple to the channel forming features described herein. Each of the channel forming feature extenders shown in FIGS. 7-9 is a plastic component extending from a first end to a second end, with the second end disposed within an interior compartment of the bioprocess bag 100. The first end of the extenders 500, 600, 700 is configured to be attached to or disposed within at least one of the plurality of connectors 140 or at least one of the plurality of ports 42 of the port attachment 40. The extenders 500, 600, 700 include an opening 510, 610, 710 disposed between the first and second ends of the channel forming feature 500, 600, 700, respectively. The extenders 500, 600, 700 also include a lower extension 520, 620, 720, respectively, extending between the opening 510, 610, 710 and the second end. As described in more detail below, the lower extension 520, 620, 720 is configured to support or otherwise connect to a channel-forming feature, such as the solid extruded plastic component 120 shown in Figures 1 and 2A-2C, or the tubular plastic component 122 shown in Figures 3A-3C. The extenders 500, 600, 700 also include an upper extension 530, 630, 730, respectively, extending between the opening 510, 610, 710 and the first end and having an internal channel that fluidly connects the opening 510, 610, 710 to at least one fitting of the bioprocess bag 100. The extensions 600, 700 also include side extensions 640, 740 that include internal channels that fluidly connect the openings 610, 710 to the internal channels of the upper extensions 630, 730. Generally, the extensions described herein further facilitate the creation of a fluid flow path so that the contents of the bioprocess bag 100 can reach the outlet.

[0034] The channel-forming feature extension 500 shown in FIG. 7 is a linear component including an opening 510 formed in its sidewall. The opening 510 is located between a lower extension 520 and an upper extension 530. The upper extension 530 includes an internal channel that fluidly connects the opening 510 to at least one connector of the bioprocess bag 100. The lower extension 520 may be a solid portion of the channel-forming feature 500 or may also include an internal channel. A channel-forming feature, e.g., a tubular plastic component 122, may be attached to the lower extension 520. If the lower extension 520 includes an internal channel, the end of the lower extension 520 remote from the opening 510 may be closed-ended or may include a plug inserted in the end to prevent fluids and / or other components from entering the internal channel. Optionally, a channel-forming feature, e.g., a solid extruded plastic component 120, may be disposed in the internal channel of the lower extension 520.

[0035] The channel-forming mechanism extension 600 shown in FIG. 8 is a Y-component, with one leg of the Y being a lower extension 620 and the other leg of the Y being a side extension 640. The side extension 640 may be shorter in length than the lower extension 620 and includes an opening 610 formed at the end of the side extension 640. The upper extension 630 includes an internal channel that fluidly connects the opening 610 to at least one connector of the bioprocess bag 100 through the internal channel of the side extension 640. The lower extension 620 may be a solid portion of the channel-forming mechanism 600 or may also include an internal channel. A channel-forming mechanism, for example, a tubular plastic component 122, may be attached to the lower extension 620. If lower extension 620 includes an internal channel, the end of lower extension 620 remote from the intersection of extensions 620, 630, 640 may be closed-ended or may include a plug inserted in the end to prevent fluids and / or other components from entering the internal channel. Optionally, a channel-forming feature, such as a solid extruded plastic component 120, may be disposed in the internal channel of lower extension 620.

[0036] 9 is a T-shaped component having a lower extension 720 and a side extension 740 extending at a 90 degree angle from an upper extension 730, which together form a straight portion of the component 700. The side extension 740 includes an opening 710 formed at the end of the side extension 740. The upper extension 730 includes an internal channel that fluidly connects the opening 710 to at least one fitting of the bioprocess bag 100 through the internal channel of the side extension 740. The lower extension 720 may be a solid portion of the channel forming component 700 or may also include an internal channel. The channel forming component, e.g., the tubular plastic component 122, may be attached to the lower extension 720. If the lower extension 720 includes an internal channel, the end of the lower extension 720 remote from the intersection of the various extensions may be closed-ended or may include a plug inserted in the end to prevent fluids and / or other components from entering the internal channel. Optionally, a channel-forming feature, such as a solid extruded plastic component 120, may be disposed in the internal channel of the lower extension 720.

[0037] According to embodiments of the present disclosure, the channel-forming feature is positioned in the bioprocess bag 100, 1100 such that the fluid flow path formed by the channel-forming feature is fluidly communicable with the outlet. Referring again to FIG. 2A as an example, the connector 140c closest to the channel-forming feature, in this case the solid extruded plastic component 120, is preferably the outlet, while any of the other connectors 140a, 140b can be the inlet. If two or more of the connectors 140 are positioned at similar distances from the channel-forming feature, any of the connectors 140 that can maintain the channel-forming feature in fluid communication with the interior compartment of the bioprocess bag 100 can be the outlet. As will be understood from the discussion herein, similar arrangements apply if the channel-forming feature is either the solid extruded plastic component 120, the tubular plastic component 122, the raised portion 124, or any other mechanism that prevents the bioprocess bag 100 from closing on itself, thereby forming a fluid flow path for the contents of the bag 100 to reach the outlet. As illustrated in Figure 2B, when the bioprocessing bag 100 is collapsed, the channel-forming feature forms a conduit that cannot be closed by application of pressure to the sheets 102, 104 of the bioprocessing bag 100. Thus, the entire interior compartment of the bioprocessing bag 100 remains in fluid communication with the outlet at all times. Similarly, with reference to Figures 3A and 3B, when at least one connector is a port fitting 40 as described herein, at least one of the plurality of ports 42 includes a channel-forming feature attached to or disposed within the port 42. This arrangement also allows the channel-forming feature to form a conduit that cannot be closed by application of pressure to the sheets 102, 104 when the bioprocessing bag 100 is collapsed. Figure 2C is a schematic diagram illustrating a top view of a bioprocessing bag having a channel-forming feature, for example, as shown in Figures 2A and 2B.2C illustrates that the channel-forming feature, in this illustration an extruded plastic component 120, prevents the sheets 102, 104 from collapsing to the point where the entire face of one sheet 102 contacts the other sheet 104, thereby preventing the sheets 102, 104 from blocking a portion of the bag 100 and / or blocking fluid and / or other components in the bag 100 from reaching the outlet. As clearly shown in FIG. 2C, a fluid flow path around the outside of the channel-forming feature is maintained at all times.

[0038] The bioprocess bag 100, 1100 also includes at least one hole 150 punched in the top welded edge of the bioprocess bag 100, 1100 and at least one hole 150 punched in the bottom welded edge of the bioprocess bag 100, 1100. As described further below, the hole 150 allows the bioprocess bag 100, 1100 to be attached in a hanging position from either the top or bottom of the bag 100, 1100. Optionally, the bioprocess bag 100, 1100 may include at least one rigid rod (not shown) sealed within the top welded edge of the bioprocess bag 100, 1100 and at least one rigid rod (not shown) sealed within the bottom welded edge of the bioprocess bag 100, 1100. Similar to the hole 150, the rigid rod allows the bioprocess bag 100, 1100 to be attached in a hanging position from either the top or bottom of the bag 100, 1100.

[0039] According to embodiments of the present disclosure, the bioprocess bag 100 may include a chromatography resin in an internal compartment of the bag 100. The chromatography resin may include, but is not limited to, a synthetic-based resin, such as styrene-DVB, an organic polymer-based resin, such as agarose or dextran, or an inorganic resin, such as silica. The chromatography resin may include a ligand, such as an affinity ligand, an ion exchange ligand, a hydrophobic interaction chromatography (HIC) ligand, a chelating ligand, a thiol ligand, or a multimodal ligand.

[0040] According to embodiments of the present disclosure, the bioprocess bag 100, 1100 may also include a sealable opening 160 that can be used to fill the bag 100 with chromatography resin. For example, as shown in FIG. 2A, the sealable opening 160 may be formed in the surface of at least one of the sheets 102, 104. The sealable opening 160 may be in the form of a port having a collar that is sealable and openable with a sealing cap. The sealable opening 160 can be made using sealing techniques known to those skilled in the art. The sealing cap may be a threaded cap having internal threads that engage with external threads on the collar to thread the cap onto the collar. A gasket may also be provided to provide a fluid-tight seal between the collar and the cap.

[0041] Also provided is a method for separating at least one target compound from a feed solution in a bioprocess bag as described herein. Figure 10 is a flow chart illustrating a method 800 described herein. It should be understood that Figure 10 is merely illustrative of an embodiment of a method as described herein, and that not all of the steps shown need be performed, and that the steps of the embodiment of the method as described herein need not be performed in any particular order, except where specified.

[0042] The method may include a step 810 of filling the bioprocess bag 100, 1100 with a chromatography resin. Filling the bioprocess bag 100, 1100 may include opening the sealable opening 160 and adding the chromatography resin to the interior compartment of the bioprocess bag 100, 1100 through the opening 160. Optionally, after the chromatography resin has been added and the sealable opening 160 is resealed, the method may further include a step 820 of sterilizing the chromatography resin in the bioprocess bag 100, 1100. Such a sterilization step may be completed using autoclaving, gamma sterilization, or any other known sterilization process. After the bioprocess bag 100, 1100 is filled, it can be stored sterile or transported to a location near a cell culture vessel, e.g., a bioreactor or other holding vessel.

[0043] According to embodiments of the present disclosure, the bioprocess bag 100, 1100 and the chromatography resin can be separately sterilizable, and the step 810 of filling the bioprocess bag 100, 1100 with the chromatography resin can include adding the chromatography resin to an internal compartment of the bioprocess bag 100, 1100 in a sterile environment. Additionally, the chromatography resin can be added to the internal compartment of the bioprocess bag 100, 1100 through an opening other than the previously described sealable opening 160. Alternatively, the chromatography resin can be added to the internal compartment of the bioprocess bag 100, 1100 through at least one of the fittings.

[0044] The method can further include a step 830 of flowing a feed solution through the bioprocess bag 100, 1100 to contact the chromatography resin in the bioprocess bag 100, 1100. The feed solution can be any fluid mixture containing two or more compounds to be separated, for example, a fermentation broth from a cell culture vessel such as a bioreactor. In this context, the term "compound" is used broadly to refer to any entity such as a molecule, chemical compound, cell, etc. The feed solution should not be passed directly from the cell culture vessel. Instead, the feed solution can be subjected to one or more steps or pretreatments, such as filtration, before flowing the feed solution through the bioprocess bag 100, 1100. Flowing the feed solution through the bioprocess bag 100, 1100 can include adding the feed solution to the bioprocess bag 100, 1100 through at least one of the connectors to contact the feed solution with the chromatography resin. Contact with the chromatography resin results in binding of the target compounds in the feed solution to the chromatography resin. As used herein, the term "target compound" refers to any compound to be separated from a feed solution. It should be understood that a target compound may be a desired product, such as a drug, diagnostic, or vaccine, or alternatively, a target compound may be a contaminant or compound typically considered an undesired product to be removed from one or more desired products. The chromatography resin is selected so that the functional group of the ligand can bind the target compound, such as an antibody / antigen, enzyme / receptor, or biotin / avidin, for example, via a "lock / key" mechanism. The target compound may be, but is not limited to, a protein, such as a membrane protein or antibody, e.g., a monoclonal antibody, a fusion protein containing an antibody or antibody fragment, such as a Fab fragment, a recombinant protein, a peptide, a nucleic acid, e.g., DNA or RNA, e.g., an oligonucleotide, a plasmid, or genomic DNA, a cell, e.g., a prokaryotic cell, a eukaryotic cell, or cell debris, a virus, a prion, a carbohydrate, or a lipid.

[0045] Optionally, the step of flowing the feed solution through the bioprocess bag 100, 1100 may be performed any number of times. For example, a first amount of feed solution may be added to the bioprocess bag 100, 1100 and contacted with the chromatography resin. After a sufficient time to allow binding of the target compounds in the feed solution with the chromatography resin, the first volume of feed solution may be dispensed from the bioprocess bag 100, 1100, e.g., through at least one of the connectors, and a next amount of feed solution may be added to the bioprocess bag 100, 1100 and contacted with the chromatography resin. Additional amounts of feed solution may be added to the bioprocess bag 100, 1100 until the binding capacity of the chromatography resin is reached.

[0046] The method can further include a step 840 of washing the chromatography resin. A wash solution can be added to the bioprocess bag 100, 1100 through one of the connectors to contact the wash solution with the chromatography resin. The wash solution can include, for example, a buffer solution. Washing the chromatography resin is performed under conditions where substantially all of the target compounds remain bound to the chromatography resin, while compounds not bound to the chromatography resin pass into the wash solution. Upon contact with the wash solution, the density of the chromatography resin allows precipitation of the chromatography resin and the formation of at least two distinct phases, the lowest of which comprises the chromatography resin. After a sufficient amount of precipitation has occurred, washing the chromatography resin can further include dispensing a lower density upper phase through at least one of the connectors. Dispensing the lower density upper phase can include pumping the lower density upper phase from the bioprocess bag 100, 1100 using a peristaltic pump. Alternatively, the step of dispensing the lower density upper phase includes applying pressure to the exterior of the bioprocess bag 100, 1100 to force the lower density upper phase out of the bioprocess bag 100, 1100. Optionally, the steps of adding wash solution and dispensing the lower density upper phase may be performed any number of times.

[0047] The method may further include a step 850 of eluting the chromatography resin. Eluting the chromatography resin may include adding an elution fluid, e.g., a solvent, capable of releasing the target compound from the chromatography resin. The elution fluid may be added to the bioprocess bag 100, 1100 through at least one of the connectors, contacting the elution fluid with the chromatography resin. Eluting the chromatography resin is performed under conditions such that substantially all of the target compound is released from the chromatography resin into the elution fluid. After contact with the elution fluid, the density of the chromatography resin allows for precipitation of the chromatography resin and the formation of at least two distinct phases, the lowest of which comprises the chromatography resin. After a sufficient amount of precipitation has occurred, eluting the chromatography resin may further include dispensing a lower density upper phase through at least one of the connectors. Dispensing the lower density upper phase may include pumping the lower density upper phase from the bioprocess bag 100, 1100 using a peristaltic pump. Alternatively, the step of dispensing the upper less dense phase includes applying pressure to the exterior of the bioprocess bag 100, 1100 to force the upper less dense phase out of the bioprocess bag 100, 1100. Optionally, the steps of adding elution fluid and dispensing the upper less dense phase may be performed any number of times.

[0048] According to embodiments of the present disclosure, it should be understood that the method steps for removing a desired product from the bioprocess bag 100, 1100 depend on the conditions selected for the separation method. For example, the desired product may be a target compound and may be removed from the bioprocess bag 100, 1100 in an elution solution. Alternatively, the desired product may not be a target compound and may be removed from the bioprocess bag 100, 1100 in a wash solution. As yet another alternative, more than one product may be the desired product. For example, a user may collect a non-target compound in the wash solution as a first desired product and collect the target compound as a second desired product. According to embodiments of the present disclosure, any of the compounds in the feed solution may be considered a desired product, and ultimately, it is up to the user to decide which compounds to collect for further use or processing and which compounds to discard.

[0049] The method can further include a step 860 of regenerating the chromatography resin. The step of regenerating the chromatography resin may include adding a buffer to the bioprocess bag 100, 1100 to prepare the chromatography resin to repeat the previous step of the method described herein of adding another feed solution to the bioprocess bag 100, 1100. Alternatively, the bioprocess bag 100, 1100 may be discarded after eluting the chromatography resin without regenerating the chromatography resin.

[0050] According to embodiments of the present disclosure, any of the steps of the method 800 described herein may include agitating the bioprocess bag 100, 1100 on a shaking, vibrating, or rocking platform. Agitating the bioprocess bag 100, 1100 in combination with step 830 of flowing a feed solution through the bioprocess bag 100, 1100 allows for efficient mixing of the feed solution and the chromatography resin, which can improve the binding rate of the target compounds in the feed solution to the chromatography resin. Agitating the bioprocess bag 100, 1100 in combination with step 840 of washing the chromatography resin allows for efficient mixing of the wash solution and the chromatography resin, which can improve the washing rate. Agitating the bioprocess bag 100, 1100 in combination with step 850 of eluting the chromatography resin allows for efficient mixing of the eluate and the chromatography resin, which can improve the release rate of the target compounds from the chromatography resin.

[0051] According to aspect (1) of the present disclosure, there is provided a method for separating at least one target compound from a feed solution, the method comprising: filling a chromatography resin into a bioprocess package including a 2D flexible container having an interior compartment, a height having an upper half and a lower half, an inlet and an outlet disposed in the same half of the 2D flexible container, and a channel-forming feature in the interior compartment of the container configured to maintain a fluid flow path fluidly connecting the interior compartment of the flexible container with the outlet; flowing the feed solution through the bioprocess package to contact the chromatography resin such that substantially all of the at least one target compound binds to the chromatography resin; and eluting the chromatography resin such that substantially all of the at least one target compound is released from the chromatography resin.

[0052] According to an aspect (2) of the present disclosure, there is provided the method according to aspect (1), wherein the step of loading the chromatography resin into the bioprocess package includes adding the chromatography resin to an internal compartment of the bioprocess package.

[0053] According to an embodiment (3) of the present disclosure, there is provided the method according to embodiment (1) or (2), wherein the feed solution comprises two or more compounds to be separated.

[0054] According to an aspect (4) of the present disclosure, there is provided the method according to any one of aspects (1) to (3), wherein the chromatography resin comprises a ligand capable of binding the target compound.

[0055] According to an aspect (5) of the present disclosure, there is provided the method of any one of aspects (1) to (4), wherein the step of washing the chromatography resin comprises adding a wash solution comprising a buffer to the bioprocess package.

[0056] According to an aspect (6) of the present disclosure, there is provided the method of any one of aspects (1) to (5), wherein washing the chromatography resin comprises forming at least two liquid phases of different densities and dispensing an upper, lower density liquid phase from the bioprocess package.

[0057] According to an embodiment (7) of the present disclosure, there is provided the method according to embodiment (6), wherein the densest liquid phase comprises a chromatography resin having at least one target compound bound thereto.

[0058] According to an eighth aspect of the present disclosure, there is provided the method of any one of the first to seventh aspects, wherein eluting the chromatography resin comprises forming at least two liquid phases of different densities and dispensing an upper, lower density liquid phase from the bioprocess package.

[0059] According to an embodiment (9) of the present disclosure, there is provided the method according to embodiment (8), wherein the lower density upper liquid phase comprises at least one target compound.

[0060] According to an aspect (10) of the present disclosure, there is provided the method of any one of aspects (1) to (9), further comprising sterilizing the chromatography resin in the bioprocess package.

[0061] According to an aspect (11) of the present disclosure, there is provided the method according to any one of aspects (1) to (10), further comprising the step of regenerating the chromatography resin.

[0062] According to a twelfth aspect of the present disclosure, there is provided the method according to the eleventh aspect, wherein the step of regenerating the chromatography resin comprises adding a buffer to the bioprocess package.

[0063] According to an aspect (13) of the present disclosure, there is provided the method according to any one of aspects (1) to (12), further comprising agitating the bioprocess package.

[0064] According to aspect (14) of the present disclosure, there is provided the method of any one of aspects (1) to (13), wherein the 2D flexible container comprises two sheets sealed along their edges to form an internal compartment.

[0065] According to an aspect (15) of the present disclosure, there is provided the method according to aspect (14), wherein the two sheets comprise a film or laminate comprising a polymer material selected from the group consisting of polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC), polyethylene terephthalate (PET), polystyrene (PS), polycarbonate (PC), polymethylpentene (PMP), polyether ether ketone (PEEK), polytetrafluoroethylene (PTFE), polyfluoroalkoxy (PFA), polychlorotrifluoroethylene (PCTFE), ethylene vinyl acetate (EVA), and derivatives thereof.

[0066] According to an aspect (16) of the present disclosure, there is provided the method of any one of aspects (1) to (15), wherein the inlet and outlet comprise connectors having internal flow paths that allow fluids and / or other components to flow into or out of the internal compartment of the flexible container.

[0067] According to an aspect (17) of the present disclosure, there is provided the method of any one of aspects (1) to (16), wherein the connector includes a face port.

[0068] According to an eighteenth aspect of the present disclosure, there is provided the method of any one of the first to seventeenth aspects, wherein the channel-forming feature comprises a solid extruded plastic component.

[0069] According to a nineteenth aspect of the present disclosure, there is provided the method of the eighteenth aspect, wherein a solid extruded plastic component is welded to a seam of the flexible container.

[0070] According to an aspect (20) of the present disclosure, there is provided the method of any one of aspects (1) to (17), wherein the channel-forming mechanism comprises a tubular plastic component.

[0071] According to a twenty-first aspect of the present disclosure, there is provided the method of the twenty-first aspect, wherein the tubular plastic component is welded to a seam of the flexible container.

[0072] According to aspect (22) of the present disclosure, there is provided the method described in aspect (20), further comprising at least two inward-facing face ports, wherein a first end of the tubular plastic component is attached to one of the at least two inward-facing face ports and a second end of the tubular plastic component is attached to another of the at least two inward-facing face ports.

[0073] According to aspect (23) of the present disclosure, there is provided the method of any one of aspects (1) to (17), wherein the channel-forming feature includes a raised portion extending from an inner surface of at least one of the two sheets.

[0074] According to an aspect (24) of the present disclosure, there is provided the method according to aspect (23), wherein the raised portion comprises a plastic component attached to an inner surface of at least one of the two sheets.

[0075] According to an aspect (25) of the present disclosure, there is provided the method according to aspect (23), wherein the raised portion comprises a textured portion on an inner surface of at least one of the two sheets.

[0076] While the present disclosure includes a limited number of embodiments, those skilled in the art will appreciate that, having the benefit of this disclosure, other embodiments may be devised that do not depart from the scope of the present disclosure.

[0077] Preferred embodiments of the present invention will be described below in detail.

[0078] Embodiment 1 1. A method for separating at least one target compound from a feed solution, comprising: a 2D flexible container including an interior compartment, a height having an upper half and a lower half, the inlet and outlet being located in the same half of the 2D flexible container; a channel-forming feature within the interior compartment of the flexible container configured to maintain a fluid flow path in fluid communication between the interior compartment of the flexible container and the outlet; Packing a chromatography resin into a bioprocess package comprising: flowing a feed solution through the bioprocess package to contact the chromatography resin such that substantially all of the at least one target compound binds to the chromatography resin; washing the chromatography resin in the bioprocess package; eluting the chromatography resin such that substantially all of the at least one target compound is released from the chromatography resin; A method comprising:

[0079] Embodiment 2 2. The method of embodiment 1, wherein said step of loading a bioprocess package with a chromatography resin comprises adding a chromatography resin to the internal compartment of the bioprocess package.

[0080] Embodiment 3 3. The method of embodiment 1 or 2, wherein the feed solution comprises two or more compounds to be separated.

[0081] Embodiment 4 4. The method of any one of embodiments 1 to 3, wherein the chromatography resin comprises a ligand capable of binding the target compound.

[0082] Embodiment 5 5. The method of any one of embodiments 1 to 4, wherein said washing the chromatography resin comprises adding a wash solution comprising a buffer to the bioprocess package.

[0083] Embodiment 6 6. The method of any one of embodiments 1 to 5, wherein the step of washing the chromatography resin comprises forming at least two liquid phases of different densities and dispensing an upper, less dense liquid phase from the bioprocess package.

[0084] Embodiment 7 7. The method of embodiment 6, wherein the densest liquid phase comprises said chromatography resin having said at least one target compound bound thereto.

[0085] Embodiment 8 8. The method of any one of embodiments 1 to 7, wherein the step of eluting the chromatography resin comprises forming at least two liquid phases of different densities and dispensing an upper, less dense liquid phase from the bioprocess package.

[0086] Embodiment 9 9. The method of embodiment 8, wherein the lower density upper liquid phase comprises the at least one target compound.

[0087] Embodiment 10 10. The method of any one of embodiments 1 to 9, further comprising sterilizing the chromatography resin in the bioprocess package.

[0088] Embodiment 11 11. The method of any one of embodiments 1 to 10, further comprising the step of regenerating the chromatography resin.

[0089] Embodiment 12 12. The method of embodiment 11, wherein said regenerating said chromatography resin comprises adding a buffer to said bioprocess package.

[0090] Embodiment 13 13. The method of any one of embodiments 1 to 12, further comprising agitating the bioprocess package.

[0091] Embodiment 14 14. The method of any one of claims 1 to 13, wherein the 2D flexible container comprises two sheets sealed along their edges to form the interior compartment.

[0092] Embodiment 15 15. The method of embodiment 14, wherein the two sheets comprise a film or laminate comprising a polymeric material selected from the group consisting of polyethylene (PE), polypropylene (PP), polyvinyl chloride (PVC), polyethylene terephthalate (PET), polystyrene (PS), polycarbonate (PC), polymethylpentene (PMP), polyetheretherketone (PEEK), polytetrafluoroethylene (PTFE), polyfluoroalkoxy (PFA), polychlorotrifluoroethylene (PCTFE), ethylene vinyl acetate (EVA), and derivatives thereof.

[0093] Embodiment 16 16. The method of any one of embodiments 1 to 15, wherein the inlet and outlet comprise connectors having internal flow paths that allow the fluid and / or other components to flow into or out of the internal compartment of the flexible container.

[0094] Embodiment 17 17. The method of any one of embodiments 1 to 16, wherein the connector comprises a face port.

[0095] Embodiment 18 18. The method of any one of the preceding embodiments, wherein the channel-forming feature comprises a solid extruded plastic component.

[0096] Embodiment 19 19. The method of embodiment 18, wherein the solid extruded plastic component is welded to a seam of the flexible container.

[0097] Embodiment 20 18. The method of any one of embodiments 1 to 17, wherein the channel-forming mechanism comprises a tubular plastic component.

[0098] Embodiment 21 21. The method of embodiment 20, wherein the tubular plastic component is welded to a seam of the flexible container.

[0099] Embodiment 22 21. The method of claim 20, further comprising at least two inward-facing face ports, wherein a first end of the tubular plastic component is attached to one of the at least two inward-facing face ports and a second end of the tubular plastic component is attached to another of the at least two inward-facing face ports.

[0100] Embodiment 23 18. The method of any one of the preceding claims, wherein the channel-forming features include raised portions extending from the inner surface of at least one of the two sheets.

[0101] Embodiment 24 24. The method of embodiment 23, wherein the raised portion comprises a plastic component attached to the inner surface of at least one of the two sheets.

[0102] Embodiment 25 24. The method of claim 23, wherein the raised portion comprises a textured portion on the inner surface of at least one of the two sheets.

Claims

1. 1. A method for separating at least one target compound from a feed solution, comprising: a pillow-shaped, 2D flexible container including an interior compartment, a height having an upper half and a lower half, an inlet and an outlet located in either half; a channel-forming feature within the interior compartment of the flexible container located near the outlet, the channel-forming feature configured to maintain a fluid flow path in fluid communication between the interior compartment of the flexible container and the outlet; Packing a chromatography resin into a bioprocess package comprising: After the filling step, sterilizing the chromatography resin in the bioprocess package by a gamma sterilization process; flowing a feed solution through the bioprocess package to contact the chromatography resin such that substantially all of the at least one target compound binds to the chromatography resin; washing the chromatography resin in the bioprocess package; eluting the chromatography resin such that substantially all of the at least one target compound is released from the chromatography resin; A method comprising:

2. 10. The method of claim 1, wherein the step of loading a bioprocess package with a chromatography resin comprises adding a chromatography resin to the interior compartment of the bioprocess package.

3. 3. The method of claim 1, wherein the feed solution comprises two or more compounds to be separated.

4. 4. The method of claim 1, wherein the chromatography resin comprises a ligand capable of binding the target compound.

5. 5. The method of claim 1, wherein washing the chromatography resin comprises adding a wash solution comprising a buffer to the bioprocess package.

6. 6. The method of claim 1, wherein the step of washing the chromatography resin comprises forming at least two liquid phases of different densities and dispensing an upper, lower density liquid phase from the bioprocess package.

7. 7. The method of claim 6, wherein the densest liquid phase comprises the chromatography resin to which the at least one target compound is bound.

8. 8. The method of claim 1, wherein the step of eluting the chromatography resin comprises forming at least two liquid phases of different densities and dispensing an upper, lower density liquid phase from the bioprocess package.

9. 9. The method of claim 1, further comprising the step of regenerating the chromatography resin.

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