Method and apparatus for packing a chromatography column assembly

Abstract

A method for filling a chromatography column with a chromatography medium, comprising the steps of: - providing a system comprising a column tube (3, 19, 21) having a closed first end (5) including an inlet / outlet (7), a medium inlet (15) near the second end of the column tube, and an adapter (9) positioned within the column tube and initially near the second end of the column tube for sliding and sealing contact with the inner surface of the column tube, the column tube and the adapter being initially arranged such that they define an internal volume and such that the medium inlet is in fluid connection with the internal volume; - connecting a medium slurry source to the medium inlet; - at least partially filling the internal volume with the medium slurry via the medium inlet; - pushing the adapter towards the first end of the column tube to reduce the internal volume such that the medium inlet is no longer in fluid connection with the reduced internal volume.

Description

Technical Field

[0001] The present invention relates to a method and an apparatus for filling a chromatography column with a chromatography medium. It also relates to a chromatography column filled with a chromatography medium according to the method, and an extended tube wall used during the filling method. Background Art

[0002] In chromatography, the use of disposable chromatography columns is now very common. In a disposable chromatography column, the supplier pre-fills the medium before delivering the column to the customer, in contrast to traditional columns that are filled by the customer at the time of use. Disposable columns are pre-filled, easy to use, and can be easily deployed by the customer. As with other disposable technologies, the column is intended to be used in a limited number of process cycles and / or activities in a dedicated process. Disposable products do not require cleaning of the equipment and associated labor, validation, and quality control efforts before and after use. In addition, disposable products can be manufactured and supplied to meet pre-defined requirements for quality control, product properties, and performance. There are various techniques for filling chromatography columns, including flow filling, pressure filling, etc. The best and most reproducible results based on a general and automatically controllable method are usually achieved by the axial compression filling technique, in which the slurry (suspension) is introduced into the column space in a first step, and in a second step, the packed bed is formed and partially compressed by the movement of an adapter. In axial compression filling, the medium slurry is a suspension of the medium with a typical slurry concentration of 40% to 70%. Therefore, a long column tube is required during the filling procedure, but after filling, more than half of the height of the column tube is usually just empty. Summary of the Invention

[0003] The object of the present invention is to provide an improved method and apparatus for filling a chromatography column.

[0004] This is achieved by a method for filling a chromatography column assembly, the method comprising the steps of:

[0005] - providing a system comprising a column tube having a closed first end including an inlet / outlet, a medium inlet near the second end of the column tube, and an adapter positioned within the column tube and initially in sliding and sealing contact with the inner surface of the column tube near the second end of the column tube, the column tube and the adapter being initially arranged such that they define an internal volume and such that the medium inlet is in fluid connection with the internal volume;

[0006] - connecting a medium slurry source to the medium inlet;

[0007] - at least partially filling the internal volume with a medium slurry via the medium inlet;

[0008] - pushing the adapter towards the first end of the column tube to reduce the internal volume such that the medium inlet is no longer in fluid connection with the reduced internal volume.

[0009] This is also achieved by a column assembly, which comprises:

[0010] - a column tube having a closed first end including an inlet / outlet, and a medium inlet near the second end of the column tube connectable to a medium slurry source; and

[0011] - an adapter positionable at a first position within the column tube near the second end of the column tube for sliding and sealing contact with the inner face of the column tube; the column tube and the adapter define an internal volume when arranged at the first position, where the medium inlet is in fluid connection with the internal volume; the adapter is movable at least to a second position to reduce the internal volume, at which second position the medium inlet is no longer in fluid connection with the reduced internal volume.

[0012] Thereby, a closed system for a filling method can be provided. This will provide the possibility of performing the filling process aseptically. If pre-sterilized components and a pre-sterilized medium slurry are used and aseptic connectors are used for connection, the entire filling method can be performed aseptically. Thereby, a sterile disposable pre-filled chromatography column can be provided. Herein, terms such as aseptic, sterilized and similar are intended to cover a range of cleanliness levels from completely aseptic (no bioburden or other contaminants) to a clean state, where there is an acceptably low level of bioburden or contamination within a closed system achieved by a controlled filling environment.

[0013] This object is also achieved by an extended tube wall arranged to be connected to the base column tube wall of the chromatography column during filling of the chromatography column according to the method. The extended tube wall includes a medium inlet.

[0014] Another object of the present invention is to provide a chromatography column filled with a chromatography medium. This is achieved by a chromatography column filled with a chromatography medium according to the method.

[0015] According to an embodiment of the present invention, the method includes providing the system and the medium slurry pre-sterilized, and providing aseptic and / or sanitary connectors to the medium inlet, the first end inlet / outlet, and / or the adapter inlet / outlet.

[0016] In an embodiment, the column assembly and its filling device are detachable, optionally leaving only the fluid path for connection to another column, thus minimizing the part of the filling device exposed to the environment outside the closed system. Thus, a method for filling a disposable chromatography column is achieved, where filling the chromatography column is aseptic.

[0017] According to an embodiment of the present invention, the method further includes the step of separating the empty part of the column tube remaining above the adapter from the rest of the column after pushing the adapter towards the first end of the column tube.

[0018] Accordingly, the filled, sterile, single-use chromatographic column is configured to have no column tube extending through the packing bed.

[0019] According to one embodiment of the present invention, the step of providing the system further includes connecting an extension tube wall to a base column tube wall, both having substantially the same inner diameter and being connected such that they form a column tube, and the step of pushing the adapter towards the first end of the column tube includes pushing the adapter to a position within the base column tube wall but outside the extension tube wall, and the step of separating the empty portion of the column tube includes disconnecting the extension tube wall from the base column tube wall.

[0020] Accordingly, a convenient method for separating the empty portion of the column tube remaining above the adapter from the rest of the column is achieved. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1a A chromatographic column according to one embodiment of the present invention in a first step of a packing procedure is shown in cross-section.

[0022] Figure 1b Shown in cross-section in a second step of the packing procedure Figure 1a of the chromatographic column.

[0023] Figure 2a A perspective view of a single-use chromatographic column filled by a method according to one embodiment of the present invention is shown.

[0024] Figure 2b Shown in cross-section Figure 2a of the single-use chromatographic column.

[0025] Figure 3 Is a flow chart of a method according to one embodiment of the present invention. DETAILED DESCRIPTION

[0026] Figure 1aThe chromatographic column assembly 1 according to an embodiment of the present invention in the first step of the filling procedure is shown in cross-section. The chromatographic column 1 includes a column tube 3 having a closed first end 5. The first end 5 includes a first bed support 4 and an inlet / outlet 7. An adapter 9 is positioned within the column tube 3 and, in this first step of the filling procedure, is in sliding and sealing contact with the inner surface of the column tube near the second end 6 of the column tube. The column tube 3 and the adapter 9 are arranged such that they define an internal volume and such that, in this first step of the filling procedure, a medium inlet 15 provided in the column tube near the second end 6 is in fluid connection with the internal volume. The adapter 9 is positioned within the column tube 3 and has a diameter that is substantially the same as the inner diameter of the column tube 3. The adapter 9 further includes a seal 11 such that a leak-proof connection between the adapter and the inner surface of the column tube 3 is provided. Additionally, the adapter is movable along the inner surface of the column tube 3. The adapter includes a second bed support 12 and an inlet / outlet 13. In the illustrated embodiment of the present invention, an air outlet 17 is also provided in the column tube 3. The air outlet is also provided near the second end 6 of the column tube 3. The air outlet 17 may be provided at the same height position as the medium inlet 15 on the column tube 3 or slightly below the position of the medium inlet 15 in order to increase the medium filling rate. In another embodiment of the present invention, since the inlet / outlet 13 in the adapter 9 can be used to discharge air, a separate air outlet is not required. It will be appreciated that the outlet 17 and the inlet / outlet 13 can be used together. Additionally, air remaining in the upper column space after filling the slurry may alternatively or separately be discharged via the medium inlet 15, which will allow the transfer of the remaining slurry in adjacent medium inlet lines and thus the recovery of the remaining slurry.

[0027] The compression frame 18 is connected to the adapter 9. In Figure 1a the embodiment shown, the compression frame 18 is arranged around the adapter inlet / outlet 13. The compression frame 18 is arranged to control the movement of the adapter 9 such that the adapter can be pushed towards the first end 5 of the column tube 3 during filling.

[0028] In one embodiment of the present invention as shown in Figure 1a the column tube 3 is divided into two parts, a base column tube wall 19 and an extension tube wall 21. The first end 20a of the base column tube wall 19 is provided with a closed first end 5. The second end 20b of the base column tube wall 19 will be connected to the extension tube wall 21. The base tube wall 19 and the extension tube wall 21 have substantially the same inner diameter and are connected to each other by a connecting device 23 during filling of the column. This can be achieved by clamping or mechanical interlocking using screws, pins or locking elements. During the first step of the filling method of the present invention, i.e., during the step of filling the column with the medium slurry, the adapter 9 is provided close to the upper end 22a of the extension tube wall 21 (also referred to as the second end 6 of the column tube 3). The lower end 22b of the extension tube wall 21 is connected to the second end 20b of the base column tube wall 19.

[0029] In this document, the column assembly 1 includes a column 3 and its associated ports 13, 15, 17, and 7, as well as an adapter 9 and filters 12 and 4. The column filling device includes a compression frame 18, and not shown: a pump; control means; and a fluid supply / outflow path. The filling device is disconnectable from the column assembly 1 at selected connectors 33, 35, 37, and 39, closing the fluid path to the column assembly and being free of contamination except at the ends of the connectors 33, 35, 37, and 39. Valves at or near the connectors 33, 35, 37, and 39 will assist in keeping the fluid path closed.

[0030] According to the present invention, there is provided a method for filling a chromatography column with a chromatography medium. A flow chart depicting the steps of the method is shown in Figure 3 and the steps will be described hereinafter:

[0031] S1: Provide a system that includes a column tube 3 having a closed first end 5 that includes an inlet / outlet 7, a medium inlet 15 near a second end 6 of the column tube 3, and an adapter 9 positioned within the column tube 3 and initially near the second end 6 of the column tube to slide and make a sealing contact with the inner surface of the column tube. The column tube 3 and the adapter 9 are initially arranged such that they define an internal volume and such that the medium inlet 15 is in fluid communication with the internal volume.

[0032] S3: Connect a medium slurry source to the medium inlet 15.

[0033] S5: Fill the internal volume defined by the column tube 3 and the adapter 9 with the medium slurry. In one embodiment of the present invention, this step includes filling the internal volume with an accurate amount of the medium slurry, and in another embodiment of the present invention, this step includes, if an air outlet 17 is provided, filling the internal volume with the medium slurry until the medium slurry begins to flow out of the air outlet 17. The advantage of this latter method is that the volume of the medium slurry provided to the column does not need to be measured, but is determined by the volume defined by the geometry of the system, which volume can be adequately controlled. Thus, the accurate volume of the medium slurry provided to the column will still be known based on the measured volume of the internal volume in the column tube below the air outlet 17.

[0034] Removal of air between the adapter and the surface of the slurry can be suitably provided. For example, this can be performed by extracting air via the air outlet 17 (if the air outlet is provided in the system) or via the adapter inlet / outlet 13 during or after the slurry filling or after the slurry has been filled via the medium inlet 15.

[0035] In one embodiment, a priming step is performed before the step of filling the internal volume with the medium slurry (step S5). The priming liquid can then be provided to the first bed support 4 to prime the first bed support. Priming of the bed support is for wetting it and / or removing air from it. The priming liquid added to the first bed support can be removed via the outlet / inlet 7 before the slurry is filled into the column, or the volume of the priming liquid provided to the bed support can be taken into account when determining how much medium slurry should be provided to the column during step S5.

[0036] S7: Push the adapter 9 towards the first end 5 to reduce the internal volume such that the medium inlet 15 (and the air outlet 17, if the air outlet is provided in the system) is no longer in fluid connection with the reduced internal volume of the column defined by the column tube 3 and the adapter 9. According to one embodiment of the present invention, the position at which the adapter should stop can be calculated by using the medium slurry concentration, the amount of medium slurry filled into the closed system, and the desired compression factor.

[0037] The axial compression filling method and the movement of the adapter 9 towards the first end 5 facilitate the formation of the packed bed into a porous structure in the first step and then facilitate the further mechanical compression of the porous structure in order to provide a stable and robust packed bed with good chromatographic analysis efficiency. In both steps, the excess liquid is removed at the inlet / outlet 7 at the closed first end 5 of the column tube 3. Generally, the volume and concentration of the medium slurry are required to calculate how much the adapter 9 should be pushed down during the filling method in order to achieve the correct compression factor. The compression factor is defined as the reciprocal of the relative volume compression of the porous medium sediment bed achieved by the axial compression of the adapter. In other words, the compression factor is the volume of the sedimented (uncompressed) medium divided by the final packed bed volume (where the medium is found in the mechanically compressed state). A typical compression factor to ensure sufficient stability and performance during operation can be in the range of 1.05 to 1.2.

[0038] Alternatively, the exact concentration of the medium slurry and / or the volume of the slurry can be adjusted to achieve the correct compression factor for the desired final bed height and final adapter position.

[0039] In an embodiment of the present invention in which the column tube 3 is divided into two parts (the base column tube wall 19 and the extension tube wall 21), the adapter 9 will be pushed into the base column tube wall 19 in this step.

[0040] S9: In one embodiment of the present invention, the adapter 9 is secured to the column tube 3 (the base column tube wall 19 in the embodiment where the column tube 3 is divided into two parts). The adapter can be secured to the column tube by welding, clamping, or mechanical interlocking, using screws, pins, or locking elements. Additional elements can be used to adapt it.

[0041] In one embodiment, the adapter is secured to the column by a press fit, e.g., by having a tube wall designed with a diameter smaller than that of the upper segment of the tube in the lower segment of the tube (with reference to Figure 1a , 1b ), such that the adapter is pushed and clamped into the lower tube as it approaches its final adapter position. The press fit can be designed to be strong enough to accommodate the final securing of the adapter, which can withstand full load and fluid pressure during use of the column in the end-user process. In another embodiment, the securing of the adapter can be a temporary securing, and the final securing can be performed in a subsequent step. The final second securing step can be achieved using a different method of securing the adapter; however, it can also be secured using the same method, but by applying different, additional, or expanded forces, displacements, or other suitable actions as required.

[0042] S11: In one embodiment of the present invention, the next step of the method consists of separating the empty portion of the column tube remaining above the adapter 9 from the rest of the column. In an embodiment where the column tube 3 is divided into two parts, the extended tube wall 21 is disconnected from the base column tube wall 19.

[0043] According to one embodiment of the present invention, the closed system and the medium slurry are provided pre-sterilized, and sterile and / or sanitary connectors are provided to at least all the inlets and outlets that are joined during the filling method, e.g., at least the medium inlet, the first end inlet / outlet, and / or the adapter inlet / outlet. Thus, the filling method can be provided as a sterile filling method in a closed system, and the filled chromatography column can be provided as a sterile column due to the sterile filling method.

[0044] According to another embodiment, the sterile column obtained from the sterile filling process can be provided with other sterile connectors that will be joined aseptically when connecting the column to the processing equipment at the point of use. In the case of using the same inlets and / or outlets of the column during both the filling method and the final processing, two or more sterile connectors can be provided to each of the corresponding inlets and / or outlets of the column. For each of the inlets and / or outlets equipped with more than one sterile connector, a valve mechanism or a manifold device can be provided to switch between more than one connector and the connected lines. For example, the inlet / outlet 7 can be used by connecting to one sterile connector during the column filling procedure. This connector can then be closed and separated by a valve. The valve can be configured to engage another (fresh) sterile connector that is connected to the processing equipment when the column is subsequently used for processing.

[0045] In another embodiment, a welding method can be used to replace the connector or the disconnecter that accommodates the sterile connection function. The welding method can also be used to achieve the closing and / or disconnection of the fluid path, e.g., between the column and the connector of the fluid path. In addition, a sterile disconnecter can be used to disconnect the sterile fluid line, e.g., to disconnect the column from the filling system after the filling process.

[0046] In a preferred embodiment, the system and the chromatographic medium are provided pre-sterilized to enable a pre-sterilized packed column by means of a sterile filling process. In another embodiment, the system and / or the chromatographic medium are provided not pre-sterilized, but preferably in known and controlled conditions and states for bioburden. In the latter embodiment, the closed system will allow maintaining the known and controlled conditions and states of the components, and in particular the chromatographic medium filled within the column volume. For example, by gamma radiation, sterilization of the packed column will be possible and facilitated by the closed filling system.

[0047] In another embodiment, the packed column can be tested and quantified after filling, for example, by residence time analysis and / or characterization of hydraulic permeability, to establish an analytical proof. If the column has been prepared from pre-sterilized components under aseptic conditions, preferably a pre-sterilized sterile filtered solution is used to perform the tests to maintain sterility. To connect the test equipment and the test fluid to the system, the plurality of sterile connections and connectors can be connected to the inlet and / or outlet of the system.

[0048] In another embodiment, the column is filled in a closed system, sterilized in a subsequent step, and then tested and / or quantified under aseptic conditions in a subsequent step before use (e.g., in biopharmaceutical production).

[0049] In one embodiment of the present invention, all parts of the column in fluid contact and also the connectors suitably provided to the column are hygienic, which means that the design will facilitate efficient cleaning and disinfection. This will provide the possibility of effectively flushing the column with a bacteriostatic storage solution before shipping and / or storage, or cleaning, storing, and reusing the column within a number of processing cycles and / or campaigns.

[0050] Figure 1b Shown in cross-section in the second step of the filling procedure Figure 1aThe chromatographic column. Here, it can be seen that the adapter 9 has been pushed downward towards the first end 5 of the column tube 3. In this embodiment, the column tube 3 is divided into a base column tube wall 19 and an extension tube wall 21, and in this embodiment, the adapter 9 will be pushed to a position within the base column tube wall 19 but outside the extension tube wall 21. Thus, the medium inlet 15 will also be passed by the adapter 9, and the medium inlet 15 will no longer be fluidly connected to the internal volume of the column defined by the column tube 3 and the adapter 9. The distance by which the adapter 9 should be pushed downward and thus the final height of the packed bed can be calculated in one embodiment by using the medium slurry concentration, the amount of medium slurry filled into the closed system, and the desired compression factor. Thus, a correctly packed medium bed will be achieved. By adjusting the medium slurry concentration and / or the amount of medium slurry filled into the closed system, the final adapter position and the packed bed height can be adjusted to the height of the base column tube 19 such that the adapter 9 will always terminate within the base column tube wall 19 and at its height and outside the extension tube wall 21 after filling. Thus, a correctly packed bed can always be achieved with the desired final bed height. Suitably, the excess fluid from the slurry will leave the column via the inlet / outlet 7 in the first end 5 during the downward movement of the adapter 9, i.e., during the filling process. The next step after filling and when the adapter 9 is in the correct position within the base column tube wall 19 is to secure the adapter to the column tube as described above and to disconnect the extension tube wall 21 from the base column tube wall 19. In another embodiment, the column tube 3 is not divided into two parts, and in this case, after filling, the part of the column tube 3 remaining above the adapter 9 can simply be cut off.

[0051] Figure 2a A perspective view of a single-use chromatographic column filled by a method according to an embodiment of the present invention is shown. This embodiment of the present invention is a chromatographic column filled by the method shown with respect to Figure 1a and 1b Here, the extension tube wall 21 has been disconnected. The base column tube wall 19 can be seen, and the adapter 9 has its inlet / outlet 13.

[0052] Figure 2b Is shown in cross-section Figure 2a Of the single-use chromatographic column.

[0053] In order to maintain Figure 2a and 2bThe sterility of the now pre-filled column shown in, it is conceivable that the now-disconnected connections 33' and 39' at ports 7 and 13 will have integral valves. For example, a simple slide gate valve can be used, or a rotatable spindle two-way or three-way valve. In addition to or as an alternative to the valve, removable or frangible seals can be used on the exposed ends of ports 7 and 13. For example, a peelable film sold by GE Healthcare under the trade name ReadyMate can be used. In this way, the column assembly can be shipped to the customer and connected to the customer's equipment without the risk of contamination. The column filling device can be reused by connecting a fresh unfilled column assembly to connectors 33, 35, 37, and 39 (discarding the extension tube 21) for the next filling procedure, again with a minimum risk of contamination.

[0054] In addition, according to the present invention, there is provided a column filling device for filling a chromatography column 1 with a chromatography medium and compressing the medium. The device is shown in Figure 1a and 1b and includes a column tube 3 having a closed first end 5 including an inlet / outlet 7 and a medium inlet 15 near a second end 6 of the column tube 3 that can be connected to a source of medium slurry. The device also includes an adapter 9 that can be positioned in a first position within the column tube 3 near the second end 6 of the column tube 3 for sliding and sealing contact with the inner surface of the column tube. The column tube 3 and the adapter 9 define an internal volume when arranged in the first position, where the medium inlet 15 is in fluid connection with the internal volume. The adapter can be moved at least to a second position to reduce the internal volume, at which second position the medium inlet 15 is no longer in fluid connection with the reduced internal volume.

[0055] In one embodiment of the present invention, the column tube 3 includes an extended tube wall 21 that includes a medium inlet 15 connected to a base column tube wall 19 including the closed first end 5, and wherein the first position of the adapter is within the extended tube wall 21 and the second position of the adapter 9 is within the base column tube wall 19.

[0056] Embodiments of the present invention provide a system that remains substantially closed when in a controlled environment and that allows disconnection only at pre-defined connection points, minimizing the risk of contamination.

Claims

1. A method for filling a chromatography column assembly (1) with a chromatography medium, comprising the steps of: - providing: a column tube (3) having a closed first end (5) including an inlet / outlet (7); a medium inlet (15) near the second end (6) of the column tube (3); and an adapter (9) positioned within the column tube (3) initially near the second end (6) of the column tube (3) for sliding and sealing contact with the inner face of the column tube, the column tube (3) and the adapter (9) being initially arranged such that they define an internal volume and such that the medium inlet (15) is in fluid connection with the internal volume; - connecting a medium slurry source to the medium inlet (15); - at least partially filling the internal volume with a medium slurry via the medium inlet (15); - pushing the adapter (9) towards the first end (5) of the column tube (3) to reduce the internal volume such that the medium inlet (15) is no longer in fluid connection with the reduced internal volume; after the adapter has been pushed towards the first end (5) and has been filled with the medium, securing the adapter (9) to the column tube (3); separating the empty portion of the column tube (3) remaining above the adapter (9) from the rest of the column.

2. The method according to claim 1, wherein The adapter includes an inlet / outlet (13).

3. The method according to claim 1 or claim 2 further comprises: Providing the system and the medium slurry as pre-sterilized and providing sterile and / or sanitary connectors to the medium inlet (15), the first end inlet / outlet (7) and / or the adapter inlet / outlet (13).

4. The method according to claim 1 or claim 2, wherein The step of providing the system further includes connecting an extension tube wall (21) to a base column tube wall (19), both having substantially the same inner diameter and being connected, which together form the column tube (3).

5. The method according to claim 4, wherein, The step of pushing the adapter (9) towards the first end (5) includes pushing the adapter (9) to a position within the base column tube wall (19) but outside the extension tube wall (21), and the step of separating the empty portion of the column tube (3) includes disconnecting the extension tube wall (21) from the base column tube wall (19).

6. The method according to claim 1 or claim 2 further comprises: Providing an air outlet (17) in the column tube (3) near the second end (6) of the column tube (3).

7. The method according to claim 1 or claim 2, wherein The step of filling the internal volume with a medium slurry includes filling the internal volume with an accurate amount of the medium slurry or filling the internal volume with the medium slurry until the medium slurry starts to flow out of the air outlet (17).

8. The method according to claim 1 or claim 2 further comprises the following steps: Calculating the position at which the adapter (9) should stop and be secured to the column tube (3) after having been pushed towards the first end (5) by using the medium slurry concentration, the amount of the medium slurry filled into the system, and the desired compression factor.

9. The method according to claim 1 or claim 2 further comprises the following steps: Adjusting the volume and / or concentration of the medium slurry filled into the internal volume of the system based on the desired position at which the adapter (9) should stop and be secured to the column tube (3) after having been pushed towards the first end (5) and / or the input of the desired compression factor.

10. The method according to claim 1 or claim 2, further comprising the steps of: A column assembly filling device (18) including one or more closable connectors (33, 35, 37, 39) is provided at the end of one or more corresponding fluid paths, and the one or more connectors are at least complementary to a first end inlet / outlet (7); At the end of the filling step, disconnect the one or more connectors to leave the corresponding closed fluid path at the filling device; and, when the claim belongs to claim 2, provide one or more closable elements (33', 39') at the adapter inlet / outlet (13) and / or at any other inlet / outlet in the column assembly (1).

11. A column assembly filled with a chromatographic medium by the method according to any one of claims 1 to 9.

12. The chromatographic column assembly according to claim 11, wherein, The chromatographic column is a sterile, single-use filled chromatographic column.

13. A column assembly (1) comprising: - A column tube (3) having a closed first end (5) including an inlet / outlet (7), and a medium inlet (15) near the second end (6) of the column tube (3) connectable to a medium slurry source; and - An adapter (9) positionable in a first position within the column tube (3) near the second end (6) of the column tube (3) for sliding and sealing contact with the inner surface of the column tube; the column tube (3) and the adapter (9) define an internal volume when arranged in the first position, wherein the medium inlet (15) is in fluid connection with the internal volume; The adapter is movable at least to a second position to reduce the internal volume, and in the second position, the medium inlet (15) is no longer in fluid connection with the reduced internal volume; After the adapter has been pushed towards the first end (5) and the medium has been filled, the adapter (9) can be fixed to the column tube (3); The empty portion of the column tube (3) remaining above the adapter (9) can be separated from the rest of the column.

14. The chromatographic column assembly according to claim 13, wherein, The adapter (9) includes an inlet / outlet (13).

15. The chromatographic column assembly according to claim 13 or claim 14, wherein, The device and the medium slurry are provided pre-sterilized, and the device further includes sterile and / or hygienic connectors provided to the medium inlet (15), the first end inlet / outlet (7), and / or the adapter inlet / outlet (13).

16. The chromatographic column assembly according to claim 13 or claim 14, wherein, The column tube (3) includes an extended tube wall (21), the extended tube wall (21) includes a medium inlet (15) connected to a base column tube wall (19) including the closed first end (5), and wherein the first position of the adapter is within the extended tube wall (21), and the second position of the adapter (9) is within the base column tube wall (19).

17. The chromatographic column assembly according to claim 13 or claim 14, wherein, The column tube (3) further includes an air outlet (17) near the second end (6) of the column tube (3).

18. The column assembly according to claim 13 or claim 14, and a column filling device, the assembly and the device having disconnectable and closable complementary fluid interconnecting paths.

Images