Bioproduct processing equipment

Abstract

The present invention relates to an apparatus 200 for processing a biological product. The apparatus 200 includes a processing column 201 having an upper column tube 202B detachably connected to a lower column tube 202A. The lower column tube 202A has a processing chamber 218 disposed therein. The apparatus 200 further includes an adapter 222 for operation within the processing column 201 to vary the volume of the processing chamber 218 within the lower column tube 202A, and a column stand 214 for supporting the adapter 222.

Description

[Technical Field]

[0001] The present invention relates generally to devices for processing biological products. More particularly, the present invention relates to improved devices incorporating processing columns with processing chambers for the production, processing, and / or separation of biological products, such as RNA for use in personalized medicine and biopharmaceutical products isolated from cell culture. [Background technology]

[0002] Various devices are known for producing or processing components of biopharmaceutical products and biologically related or derived products used in various processes, for research supplies, etc. Many of the desired final biological products are produced or processed using devices within process chambers formed within process columns.

[0003] For example, commercially available Cytiva Life Sciences® compatible oligo columns can be used for oligonucleotide synthesis and are designed for running the process in conjunction with the Acta® OligoPilot® in addition to synthesizers.

[0004] Other device-based columns are also known, for example, where the columns can be used in chromatography-based bioproduct separation systems or bioprocessing separation systems, see, e.g., WO 2013 / 191628 and WO 2015 / 088427, the contents of which are incorporated herein by reference to the fullest extent permitted.

[0005] However, while various adaptable column devices have been available for a long time, and Cytiva Life Sciences® adaptable oligo columns in particular are high quality and well-established products, it is desirable to provide even more improved equipment that is safer to operate, easier to use and maintain, and has increased potential production capacity. Summary of the Invention

[0006] Therefore, the present invention is provided as defined by the appended claims.

[0007] In a first aspect, the present invention thus relates to an apparatus for processing a biological product, the apparatus comprising a processing column having an upper column tube detachably connected to a lower column tube having a processing chamber disposed therein, an adapter operable within the processing column to vary the volume and / or bed height of the processing chamber within the lower column tube, and a column stand for supporting the adapter are also provided.

[0008] In another aspect of the invention, there is provided a column processing module for an apparatus having a lower column tube carrying a process chamber for holding a biological product, a support for holding the lower column tube in a substantially horizontal position, and the lower column tube for use in the apparatus.

[0009] The multi-section column design, with its column stand and adapter, provides a device that is easy to clean and maintain. The design also allows sections of the processing column to be removed for washing or extracting product, while separate replacement column sections can be installed. Therefore, start-up time for processing or production can be increased by constantly replacing column processing modules, which themselves can optionally be pre-filled with various sterile materials needed for processing or production.

[0010] Another advantage of various aspects and embodiments of the present invention is that removal and / or replacement of various parts of the device can be done without lifting, so that a compact or small footprint or easy to use or maintain device is provided. [Brief explanation of the drawings]

[0011] [Figure 1] FIG. 1 shows a column-based device for chromatographic separation processes according to the prior art. [Figure 2] FIG. 2 shows the column-based device of FIG. 1 with an internally mounted adapter according to the prior art. [Figure 3] 3A and 3B show an apparatus for processing bioproducts in accordance with an embodiment of the present invention. [Figure 4] Figures 4A, 4B and 4C illustrate the use of the apparatus of Figures 3A and 3B in a column process run mode. [Figure 5] Figures 5A, 5B and 5C illustrate the use of the apparatus of Figures 3A and 3B during a bottom separation operation. [Figure 6] Figures 6A, 6B and 6C illustrate the use of the device of Figures 3A and 3B during an apical separation operation. [Figure 7] 7A, 7B and 7C show a column processing module for use in the apparatus of FIGS. 3A and 3B in accordance with an embodiment of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0012] 1 shows a column-based device 101 for a chromatographic separation process according to the prior art. A tubular housing 102 is provided in which a fluid space 118 and a bed space 120 are defined. An adapter 122 is further provided for providing a layer 124 of packed particulate media in the bed space 120.

[0013] The tubular housing 102, top end 104, and bottom end 106 are secured together by tension bolts to form a fluid-tight seal. The tubular housing 102 and top and bottom ends 104, 106 are generally constructed from a solvent-resistant material, such as stainless steel or a high-strength plastic material, such as polypropylene. Where the column-based device 101 is to be used for the separation of biologically active substances, the material is biologically inert so that it does not elicit an immune response in humans. An adapter rod 110 extends into an opening 112 in the top end 104 and into the tubular housing 102. The column-based device 101 is also mounted on a frame 114, which is provided with legs 116, so that the column-based device 101 can be placed on the floor in a stable position.

[0014] The column-based device 101 is shown with the bottom end 106 removed and the adapter 122 downward relative to a position where a portion of the adapter 122 still resides inside the cylindrical housing 102 of the column-based device 101 so that compressed fluid held inside the column-based device 101 on the adapter 122 cannot escape therefrom.

[0015] In this lower position, the first slide ring 144a of the adapter 122 is positioned to be disposed on the inner surface of the cylindrical housing 102 to provide a seal between the adapter 122 and the cylindrical housing 102. In the first, lower adapter position, the cavity 146 disposed on the surface of the adapter 122 is located outside the cylindrical housing 102, and the second slide ring 144b covers the cavity 146, such that the cavity 146 can be accessed from outside the column-based device 101 after removing the second slide ring 144b.

[0016] The cavity 146 is located closer to the end surface 141 of the adapter 122 than to the top surface 143. A securing means (not shown) can be attached and detached through the cavity 146 for removing the filter from the adapter 122. A support trolley 170 is located below the adapter 122 so that the filter can be placed on the trolley 170 when the filter is removed from the adapter 122.

[0017] Figure 2 shows a perspective view of the column-based device 101 of Figure 1 having an adapter 122 disposed therein, according to the prior art. The adapter 122 is used in conjunction with a filter (not shown) and a distributor plate (not shown) to pack the layer of packaging material inside the cylindrical housing 102. The distributor plate distributes fluid inside the column-based device 101, while the filter prevents particles from escaping, and the filter prevents particles from penetrating from the layer of packaging material into holes or openings inside the distributor plate.

[0018] The tubular housing 102 and ends 104, 106 form a fluid space 118 and a bed space 120, and both spaces 118, 120 are fluid-tight and can withstand high operating pressures. A wide range of column volumes is also possible, typically ranging from 0.1 liters to 2000 liters. The bed space 120 is defined by the tubular housing 102, the bottom end 106, and an adapter 122 connected to the adapter rod 110.

[0019] The bed space 120 is filled with a layer of packing material 124, which is generally particulate in nature and composed of a porous medium. A liquid mobile phase is arranged to enter through an inlet 126 at the end of the adapter rod 110, flowing through a central channel 128 within the adapter rod 110 and toward the adapter 128. The liquid mobile phase then travels through the layer of packing material 124 and is finally removed through an outlet 130 at the bottom end 106. Typically, the porous medium enclosed within the column 101 as a packed bed 124 is generally formed by consolidating a suspension of discrete particles, known as a slurry, which is poured, expelled, or drawn into the column-based device 101 from a bore or nozzle 132 located inside the tubular housing 102.

[0020] The layer 124 of packed particulate media is achieved by downward movement of the adapter 122 to compress the layer 124 between the adapter 122 and the bottom end 106. The compressive force and downward movement of the adapter 122 is achieved by supplying pressurized fluid to the fluid space 118 above the adapter 122. The fluid, such as water, is poured into the fluid space 118 through a valve 134 located inside the top portion 104.

[0021] The above-described prior art column-based device 101 provides improved maintenance of chromatography columns, particularly those used in large-volume, industrial-scale chromatography, by reducing the need to use heavy lifting equipment, such as hoists or cranes, to dismantle the column. However, such a process is still relatively time-consuming and labor-intensive because it requires removal of the bottom end 106, and is therefore generally best suited for infrequently required maintenance operations, such as replacing a filter or seal, such as adapter 122.

[0022] 3A and 3B show an apparatus 200 for processing a biological product according to an embodiment of the present invention.

[0023] Figure 3A is a schematic diagram of an apparatus 200 in cross section, which incorporates a processing column 201 comprising an upper column tube 202B that is removably coupled to a lower column tube 202A via a mechanism described below in connection with Figure 3B.

[0024] The lower column tube 202A is coupled to a chamber base plate 231, thereby defining a processing chamber 218. The processing chamber 218 can be used to produce and / or process a variety of biological products, such as DNA, RNA, and mAb-related products, which can also be processed or produced under generally aseptic or sterile conditions.

[0025] Apparatus 200 further includes an adapter 222 for operation within processing column 201 to vary the volume of processing chamber 218 within lower column tube 202A. Adapter 222 includes an adapter rod 210 connected to a lower chamber casing 225. Lower chamber casing 225 supports a flow distribution or filter plate 229. Adapter rod 210 penetrates a sealing arrangement provided in an opening in upper plate 223 such that adapter rod 210 can slide through the opening. The outer surface of upper plate 223 is removably coupled to the upper end of upper column tube 202B in a fluid-tight arrangement. Upper plate 223 and lower chamber casing 225 together define a fluid-tight hydraulic chamber 227 therebetween.

[0026] Hydraulic fluid (e.g., pressurized water) can thus be introduced into and / or removed from hydraulic chamber 227 through ports (not shown) in upper plate 223 to move lower chamber casing 225 to a desired position within processing column 201. The volume of processing chamber 218 can thus be adapted to the volume required by using column adapter 222, for example, to accommodate a particular support used, a desired scale of operation, etc. For specific applications, a variable bed height within processing chamber 218 can also be provided to allow for variations in processing scale, etc.

[0027] The apparatus 200 further includes a column stand 214 for supporting the adapter 222. The column stand 214 includes a frame 254 that generally surrounds the processing column 201. Optionally, the frame 254 may provide additional support for the upper column tube 202B, for example, via a locking mechanism, bolts, support brackets, etc. An axially aligned central through-hole is provided in the upper portion of the frame 254 to allow the adapter rod 210 of the adapter 222 to pass through the through-hole. A rod locking mechanism 250 is provided adjacent the through-hole in the frame 254. The rod locking mechanism 250 is operable to secure the adapter rod 210 at various positions relative to the frame 254. The rod locking mechanism 250 may incorporate, for example, a brake mechanism or a similar mechanism that can be operated either manually and / or automatically.

[0028] A top plate holder 252 is mounted inside the frame 254. The top plate holder 252 optionally includes a coupling mechanism (not shown) for connecting with the upper plate 223 when the upper plate 223 is attached or detached from the upper end of the upper column tube 202B.

[0029] 3A, the lower column tube 202A, as part of the column treatment module 260, is mounted on a support 270, which is provided to hold the lower column tube 202A in a substantially horizontal position during use of the apparatus 200. The support 270 is preferably, but not necessarily, connected to a plurality of wheels 262, which allow the column treatment module 260 to be easily moved across the floor surface, for example, of a bioprocessing or production facility.

[0030] The column processing module 260 can thus be easily removed from the apparatus 200 for further processing and / or cleaning and replaced with a similar column processing module 260, e.g., pre-loaded with various materials, components, resins, beads, etc. Therefore, bioprocessing can be sped up by using multiple column processing modules to provide higher production throughput when using various embodiments of the present invention.

[0031] 3B shows an enlarged view of the detachable connection for joining the upper column tube 202B with the lower column tube 202A. The upper column tube 202B has a radially outwardly disposed peripheral notch 203. The lower column tube 202A has a radially outwardly disposed peripheral groove 205 for receiving the peripheral notch 203 therein. The above arrangement allows for precise and stable alignment of the upper and lower column tubes 202A, 202B.

[0032] The upper column tube 202B further includes a radially inwardly disposed peripheral O-ring seal 207. The weight of the upper column tube 202B encourages the O-ring seal 207 to seal against the upper end surface of the lower column tube 202A when the upper and lower column tubes 202A, 202B are in a stacked arrangement.

[0033] Various other detachable connections for coupling the upper column tube 202B and the lower column tube 202A will also be apparent to those skilled in the art. For example, the upper column tube 202B may include a notch and the lower column tube 202A may include a groove or grooves or notches, etc., in various locations, one or more sealing arrangements or sealing components may be provided in various locations on one or more of the upper and / or lower column tubes, etc.

[0034] 4A, 4B, and 4C illustrate the use of the apparatus 200 of FIGS. 3A and 3B in a column process run mode.

[0035] 4A shows the apparatus 200 in a first operating position. The lower chamber casing 225 is sealed to the interior of the upper column 202B by upper and lower O-rings 233 and is positioned generally adjacent to the upper plate 223. Another O-ring 233 also initially seals the peripheral surface of the flow distribution or filter plate 229 within the upper column tube 202B. The provision of the O-ring 233 allows operation of the adapter 222 above the soft joint between the upper and lower column tubes 202A, 202B without any substantial leakage. The column processing module 260 further includes a bioproduct 209 within the process chamber 218, with the rod locking mechanism 250 in an unlocked position.

[0036] In various embodiments, a slurry inlet may be provided in the upper column tube 202B. A slurry inlet or outlet may also be provided in the lower region of the lower column tube 202A.

[0037] 4B shows the apparatus 200 in a second operating position. In the second operating position, hydraulic fluid is introduced into the hydraulic chamber 227 through an inlet or valve (not shown) provided in the upper plate 223. An additional outlet or valve (not shown) may also be provided in the upper plate 223. The hydraulic fluid causes the hydraulic chamber 227 to expand the lower chamber casing 225, together with the flow distribution or filter plate 229 attached thereto, towards the lower column tube 202A and away from the upper plate 223.

[0038] 4C shows the apparatus 200 in a third or final operating position. In the final operating position, the lower O-ring 233 of the chamber casing 225 and the O-ring 233 provided with the flow distribution or filter plate 229 are pressed into the lower column tube 202A. The flow distribution or filter plate 229 and the chamber base plate 231 are thus brought into close proximity. Furthermore, as the chamber casing 225 is pressed into the process chamber 218, a valve (not shown) therein is opened to allow the bioproduct 209 to be extracted. Alternatively, in various embodiments, the bioproduct 209 may be extracted through the slurry outlet.

[0039] During operation, for example, during oligo processing, the upper and lower O-rings 233 mounted on the lower chamber casing 225 do not necessarily move over the joint between the upper and lower column tubes 202A, 202B during the process. During the process (e.g., used during peptide synthesis, molecular synthesis, etc.), molecular chains may build up on substrates such as beads. As these molecular chains grow, they occupy increased space, subsequently requiring increased volume or pressure to be maintained within the processing chamber 218. The apparatus 200 can therefore be adapted to accommodate such volume or pressure requirements, and therefore may not need to follow all of the steps shown in Figures 4A-4C.

[0040] 5A, 5B and 5C illustrate the use of the apparatus 200 of FIGS. 3A and 3B during a bottom separation operation.

[0041] 5A shows the apparatus 200 in a first operating state. The lower chamber casing 225 is sealed within the upper column tube 202B by upper and lower O-rings 233 and is positioned generally adjacent the upper plate 223. Another O-ring 233 also initially seals the peripheral surface of the flow distribution or filter plate 229 within the upper column tube 202B. The column processing module 260 is shown with the bioproduct 209 within the process chamber 218, and the rod locking mechanism 250 is in an initial, unlocked state.

[0042] 5B shows the device 200 in a second operating configuration in which the rod locking mechanism 250 is engaged such that the adapter rod 210 is fixed relative to the column stand 214. The rod locking mechanism 250 may be manually engaged (e.g., by use of a solenoid or hydraulic actuator) and / or automatically engaged as part of a remotely controlled operation.

[0043] Once the rod locking mechanism 250 is engaged, hydraulic fluid is introduced into the hydraulic chamber 227. The introduction of hydraulic fluid into the hydraulic chamber 227 causes the upper plate 223 to be pulled up towards the rod locking mechanism 250. Because the upper plate 223 is connected to the upper column tube 202B, the latter also pulls up, thereby pulling the upper column tube 202B away from the lower column tube 202A. This causes the upper column tube 202B to move axially away, while the lower column tube 202A remains in its original position within the column processing module 260.

[0044] 5C shows the apparatus 200 in a third operating configuration, in which the rod locking mechanism 250 remains engaged while the column treatment module 260 is removed from the interior of the lower volume 235 defined by the column stand 214. Preferably, but not necessarily, the column treatment module 260 is of the type shown in FIGS. 7A to 7C (see below), which includes a plurality of wheels 262 provided to assist in moving the column treatment module 260. In the third apparatus configuration, the flow distribution or filter plate 229 is also readily accessible, allowing for easier cleaning, maintenance, etc.

[0045] 6A, 6B, and 6C illustrate the use of the apparatus 200 of FIGS. 3A and 3B during an apical separation operation.

[0046] 6A shows the apparatus 200 in a first operating position. The lower chamber casing 225 is sealed within the upper column tube 202B by upper and lower O-rings 233 and is positioned generally adjacent the upper plate 223. Another O-ring 233 also initially seals the peripheral surface of the flow distribution or filter plate 229 within the upper column tube 202B. The column processing module 260 is shown with the bioproduct substituted fluid 209' inside the process chamber 218 and the rod locking mechanism 250 in a first unlocked state.

[0047] 6B shows the apparatus 200 in a second operating state. In the second operating state, the upper plate 223 is first separated from the upper column tube 202B. The process chamber 218 is then filled with the bioproduct replacement fluid 209′, and the entire adapter 222 is raised. Once the upper plate 223 is positioned adjacent to the top plate holder 252, the rod locking mechanism 250 is engaged to prevent the adapter rod 210 from moving relative to the column stand 214. Optionally, the top plate holder 252 may include a mechanism for removably retaining the upper plate 223 thereto to prevent it from falling if the rod locking mechanism 250 fails or accidentally disengages. Additionally or alternatively, various bolts, removable fasteners, etc. may be used to secure the upper plate 223 to the top plate holder 252.

[0048] 6C shows the apparatus 200 in a third operating state. In the third operating state, the bioproduct surrogate fluid 209' is discharged from the process chamber 218 and the lower chamber casing 225, and the connected flow distribution or filter plate 229 is lowered into the upper column tube 202B. The adapter rod 210 remains in place because the rod locking mechanism 250 is still engaged. The upper plate 223 remains engaged with the top plate holder 252 inside the upper volume of the column stand. Therefore, in this state, the upper plate 223, the interior of the lower chamber casing 225, and the top of the adapter 222 are available for maintenance.

[0049] 7A, 7B, and 7C illustrate a column processing module 260 for use in the apparatus 200 of FIGS. 3A and 3B according to various embodiments of the present invention.

[0050] 7A shows a cross-sectional view of column processing module 260. Column processing module 260 includes lower column tube 202A and chamber base plate 231, which together define process chamber 218. Process chamber 218 can contain one or more bioprocessing materials for processing or producing a bioproduct. The materials can be pre-filled or already filled therein and further provided, and can optionally be sterile / aseptic and / or filled.

[0051] Both the lower column tube 202A and the chamber base plate 231 are connected to a support 270 that can be used to maintain the lower column tube 202A and / or the chamber base plate 231 in a substantially horizontal position. Furthermore, the support 270 is rotatably coupled to first and second supports 263 provided on a chassis 275 via at least one tilt mechanism 264.

[0052] The chassis 275 further incorporates a plurality of wheels 262 that allow the column processing module 260 to be easily moved across a floor surface, with or without any contents in the processing chamber 218 .

[0053] 7B shows a side view of the column processing module 260 with the lower column tube 202A and chamber base plate 231 in a substantially horizontal position. In this position, one or more tilt mechanisms 264 may be in a locked position to maintain the horizontal position when the column processing module 260 is moved.

[0054] 7C shows a side view of the column processing module 260 in a tilted position. If locking is provided, one or more tilt mechanisms 264, along with the lower column tube 202A and the chamber base plate 231 supported thereon, can be unlocked before the support 270 is rotated away from the horizontal position.

[0055] The lower column tube 202A can be optionally released through a side port (not shown) therein and / or manually. This particular embodiment also allows the lower column tube 202A to rotate to assist in discharging its contents to the outside.

[0056] While various preferred embodiments may employ tilt mechanisms therein, those skilled in the art will understand that the present invention is not so limited. For example, various column processing module designs are apparent, including those that have a substantially fixed orientation relative to the processing chamber.

[0057] Thus, various embodiments of the present invention may be configured to have a process chamber that is easier to clean or maintain, easier to transport or replace during use, allow for no-lift operation, allow for efficient part replacement of the device so that the original part can be cleaned or inspected while being replaced with another part, use flow-through reactor technology, provide for packing or pre-packing of useful solid support materials, be solvent resistant, have a simple and robust design, and / or maximize the "up time" of the bioproduction device, etc.

[0058] Where large product or bioprocessing systems (e.g., having a capacity of 1000 liters, 2000 liters, etc.) are used, the use of no-lift embodiments further improves the safety aspect of operation by avoiding the need to lift heavy, swingable components such as reactor lids. Safe plant operation is further enhanced in areas where any hazardous chemicals may remain after processing operations, as shorter, movable column sections more easily allow for disposal or removal of hazardous products, thereby making it easier to access the bottom of shorter column sections, for example, for spatulas, vacuum aspirators, etc.

[0059] Those skilled in the art will also recognize that many materials may be used to construct the various components or portions of the apparatus provided in accordance with the present invention. For example, various solvent-resistant materials, stainless steel materials, and / or plastic materials, such as polypropylene, may be used as appropriate for any desired end application.

[0060] Various aspects and embodiments of the present invention have been described herein. However, those skilled in the art will recognize that various modifications may be made to still embody the envisioned inventive concepts. For example, those skilled in the art will recognize that various elements of both the prior art and the embodiments described herein may be combined to yield still further embodiments of the present invention.

[0061] Furthermore, it should be noted that all previously mentioned patents, patent applications and / or commercially available products disclosed are hereby incorporated by reference in their entirety for all purposes. [Explanation of symbols]

[0062] 101 Column-based Devices 101 Column 102 Tubular housing 104, 106 End 104, 106 Top end 104 Vertex 110 Adapter Rod 112 Opening 114 frames 116 Legs 122 Adapter 124 Filled bed 126 Entrance 128 Center Channel 128, 222 adapter 130 Exit 132 nozzles 134 Valve 141 End surface 143 Top surface 144a First slide ring 144b Second slide ring 146 Cavity 170 Trolley 200 equipment 201 Treatment column 202A, 202B Lower column tube 202B Upper column pipe 203 Peripheral notch 205 Peripheral ditch 207 O-ring seal 210 Adapter Rod 214 Column Stand 218 Processing Chamber 218 Process Chamber 223 Upper Plate 225 Chamber Casing 227 Hydraulic Chamber 229 Filter Plate 231 Chamber base plate 233 O-ring 250 Rod locking mechanism 252 Top Plate Holder 254 frames 260 Column Processing Module 262 Wheels 263 First support part, second support part 264 Tilt mechanism 270 Support part 275 chassis

Claims

1. An apparatus (200) for bioproduct processing, comprising: a processing column (201) comprising an upper column tube (202B) detachably coupled to a lower column tube (202A) having a processing chamber (218) therein; an adapter (122) operable within the processing column (201) to vary the volume of the processing chamber (218) within the lower column tube (202A); a column stand (214) for supporting the adapter (222); the lower column tube (202A) is mounted as part of a column treatment module (260) on a support (270) for holding the lower column tube (202A) in a substantially horizontal position during use of the apparatus (200); The apparatus (200), wherein the column treatment module (260) further comprises a wheel (262) or a plurality of wheels (262) for enabling the column treatment module (260) to move on a floor surface, and / or at least one tilt mechanism (264) for moving the lower column tube (202A) to and from the substantially horizontal position.

2. The apparatus (200) of claim 1, wherein the column stand (214) comprises a frame (254).

3. The apparatus (200) of claim 2, wherein the frame (254) comprises a top plate holder (252).

4. The apparatus (200) of any one of claims 1 to 3, comprising a rod locking mechanism (250) for holding the adapter (222) in a raised position.

5. 5. The apparatus of claim 1, wherein the adapter is hydraulically actuatable and comprises an adapter rod removably connectable to a lower chamber casing through an opening in an upper plate such that the adapter rod is slidable through the opening; an outer surface of the upper plate is removably coupleable with an upper end of the upper column tube; and the upper plate and the lower chamber casing define a fluid-tight hydraulic chamber between the upper plate and the lower chamber casing.

6. A column processing module (260) for an apparatus (200) described in any one of claims 1 to 5, comprising: a lower column tube (202A) providing a process chamber (218) for holding a bioproduct (209); and a support (270) for holding the lower column tube (202A) in a substantially horizontal position.

7. 7. The column treatment module (260) of claim 6, further comprising at least one wheel (262) for enabling the column treatment module (260) to move across a floor surface.

8. 8. The column treatment module (260) of claim 6 or 7, further comprising at least one tilt mechanism (264) for moving the lower column tube (202A) to and from the substantially horizontal position.

9. The column treatment module (260) of any one of claims 6 to 8, further comprising one or more bio-treatment materials for treating and / or producing the pre-loaded bio-product (209).

10. The column treatment module (260) according to any one of claims 6 to 9, wherein at least a part of the column treatment module (260) is supplied in a sterile or aseptic condition.

11. A lower column tube (202A) for use in an apparatus (200) according to any one of claims 1 to 5, or for use with a column treatment module (260) according to any one of claims 6 to 10, having the process chamber (218) for holding the bioproduct (209) provided therein.

12. 12. The lower column tube (202A) of claim 11, further comprising one or more bioprocessing materials for processing and / or producing the bioproduct (209) pre-loaded in the process chamber (218).

13. The lower column tube (202A) according to claim 11 or 12, wherein the lower column tube (202A) is sterile or aseptic.

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