US-12616918-B2 - Connection device for a separation system such as a chromatography system

US12616918B2US 12616918 B2US12616918 B2US 12616918B2US-12616918-B2

Abstract

A connection device ( 1; 101 ) configured for connecting a separation system ( 3 ) with a separation device ( 5 ), wherein a fluid can be flowed from a separation system outlet connection ( 19 ), through a bypass fluid path ( 27 ) of the connection device to the separation system inlet connection ( 15 ) while a connected separation device ( 5 ) is by passed. For achieving this at least one of an inlet and an outlet valve ( 31, 33 ) provided in the connection device is provided in a closed state and at least one bypass valve ( 35; 35 a, 35 b ) provided in the connection device is provided in an open state.

Inventors

Klaus Gebauer
Andreas Lundin
Fredrik Lundström

Assignees

CYTIVA SWEDEN AB

Dates

Publication Date: 20260505
Application Date: 20190820
Priority Date: 20180831

Claims (20)

1 . A connection device for connecting a biopharmaceutical separation system and a separation device, said connection device comprising: a separation device inlet connection connected to a separation device inlet; a separation device outlet connection connected to a separation device outlet; a biopharmaceutical separation system inlet connection connected to a biopharmaceutical separation system inlet; a biopharmaceutical separation system outlet connection connected to a biopharmaceutical separation system outlet; a first fluid path connecting the biopharmaceutical separation system inlet connection with the separation device outlet connection and allowing fluid flow from the separation device outlet connection towards the biopharmaceutical separation system inlet connection; a second fluid path connecting the biopharmaceutical separation system outlet connection with the separation device inlet connection and allowing fluid flow from the biopharmaceutical separation system outlet connection towards the separation device inlet connection; a bypass fluid path connecting the biopharmaceutical separation system inlet connection with the biopharmaceutical separation system outlet connection and allowing fluid flow from the biopharmaceutical separation system outlet connection towards the biopharmaceutical separation system inlet connection; an inlet valve provided in the second fluid path in connection with the separation device inlet connection, said inlet valve being operable to provide an open state allowing fluid flow through the separation device inlet connection and a closed state preventing fluid flow through the separation device inlet connection; an outlet valve provided in the first fluid path in connection with the separation device outlet connection, said outlet valve being operable to provide an open state allowing fluid flow out through the separation device outlet connection and a closed state preventing fluid flow through the separation device outlet connection; and at least one bypass valve provided in the bypass fluid path, said at least one bypass valve being operable to provide an open state allowing fluid flow through the bypass fluid path and a closed state preventing fluid flow through the bypass fluid path, wherein a fluid can be flowed from the biopharmaceutical separation system outlet connection, through the bypass fluid path to the biopharmaceutical separation system inlet connection while a connected separation device is bypassed when at least one of the inlet and outlet valves is provided in a closed state and the at least one bypass valve is provided in an open state; wherein said at least one bypass valve is positioned in the bypass fluid path at a distance from the first and/or second fluid path of no more than 3 times a diameter of the first, the second and/or the bypass fluid path; wherein the separation device is a chromatography column or a stack of chromatography units, and wherein the biopharmaceutical separation system is a chromatography system; wherein the fluid paths are formed using pre-sterilized plastic tubing; and wherein the bypass fluid path is configured to remove air from the biopharmaceutical separation system without passing air through a chromatography bed of the separation device.
2 . The connection device according to claim 1 , wherein the at least one bypass valve is of diaphragm type.
3 . The connection device according to claim 1 , wherein said inlet and outlet valves are of diaphragm type.
4 . The connection device according to claim 1 , wherein the inlet and outlet valves are positioned at a distance from junctions in between the first and second fluid paths and the bypass fluid path, of no more than 3 times, or 2 times, or 1 times a diameter of the first, the second and/or the bypass fluid line.
5 . The connection device according to claim 1 , wherein the separation device inlet and outlet connections are provided with aseptic connectors.
6 . The connection device according to claim 1 , wherein the biopharmaceutical separation system inlet and outlet connections are provided with aseptic connectors.
7 . The connection device according to claim 1 , wherein said inlet valve, said outlet valve and said at least one bypass valve are manually controllable into open and closed states.
8 . The connection device according to claim 1 , wherein the connection device comprises at least one monitoring device which is connected to the inlet valve, the outlet valve and/or to the at least one bypass valve and which monitoring device shows the states of the inlet valve, the outlet valve and the at least one bypass valve.
9 . The connection device according to claim 1 , wherein the connection device further comprises at least one sensor arranged in the connection device for detecting an open and/or closed state of at least one of the inlet valve, the outlet valve or the at least one bypass valve.
10 . The connection device according to claim 1 , wherein the connection device comprises a combination control device which is connected to both the inlet valve, the outlet valve and to the at least one bypass valve and which in a first position controls the inlet valve and the outlet valve to be in open states and the at least one bypass valve to be in a closed state and which in a second position controls the inlet valve and the outlet valve to be in closed states and the at least one bypass valve to be in an open state.
11 . The connection device according to claim 1 , wherein the at least one bypass valve is a single bypass valve, and wherein said inlet valve said outlet valve and said single bypass valve are provided together in one valve assembly part.
12 . The connection device according to claim 1 , wherein the at least one bypass valve includes a first bypass valve and a second bypass valve, and wherein the connection device comprises an inlet valve assembly part comprising the inlet valve and the second bypass valve and an outlet valve assembly part comprising the outlet valve and the first bypass valve, wherein said bypass fluid path is provided between the first and the second bypass valves.
13 . The separation device comprising a separation device inlet and a separation device outlet and a connection device according to claim 1 connected to the separation device inlet and the separation device outlet.
14 . The separation device according to claim 13 , which separation device is pre-packed with a bed of chromatography media.
15 . The separation device according to claim 13 , wherein the connection device is connected to the separation device inlet and the separation device outlet through barbed connections, Barblock connections, TC connections or welded connections.
16 . The separation device according to claim 13 , wherein said connection device is integral with the separation device.
17 . The separation device according to claim 16 , wherein said bypass fluid path is provided integral with an end unit of the separation device or in the form of at least one header for said stack of units, said header including said at least one bypass valve.
18 . The separation device according to claim 13 , wherein said biopharmaceutical separation system inlet and outlet connections of the connection device are provided with aseptic connectors.
19 . The biopharmaceutical separation system comprising a biopharmaceutical separation system inlet and a biopharmaceutical separation system outlet and a connection device according to claim 1 connected to the biopharmaceutical separation system inlet and the biopharmaceutical separation system outlet.
20 . The biopharmaceutical separation system according to claim 18 , wherein the connection device is connected to the biopharmaceutical separation system inlet and the biopharmaceutical separation system outlet through barbed connections, Barblock connections, TC connections or welded connections.

Description

CROSS REFERENCE TO RELATED APPLICATIONS This application claims the priority benefit of PCT/EP2019/072307, filed on Aug. 20, 2019, which claims the benefit of Great Britain Application No. 1814213.3, filed on Aug. 31, 2018, the entire contents of which are incorporated by reference herein. TECHNICAL FIELD OF THE INVENTION The present invention relates to a connection device for connecting a separation device to a separation system, such as for example a chromatography column to a chromatography system. It also relates to a chromatography column and to a separation system such as a chromatography system. RELATED ART Pre-packed chromatography columns are important separation devices in biopharmaceutical manufacturing. They may be used for manufacturing multiple drug products and thus be used in different processes, however, preferably they are used for manufacturing exclusively a single biopharmaceutical drug product to avoid the need for extensive cleaning and sanitization arising from the risk for cross-contamination when using the same column for producing different drug products. Pre-packed columns are therefore often used as single-use columns and used with other single-use technology products, such as single-use flow paths in chromatography systems and single-use fluid storage bags, single-use tubing etc. As described, the advantage of using single-use technology (SUT) fluid handling equipment is primarily that cross-contamination in between production batches and campaigns is reduced or completely eliminated when the SUT equipment is used for a single drug product only. The SUT equipment is disposed of after use, which can be after a single run, batch or campaign comprising multiple runs and batches. When providing SUT equipment pre-sterilized or bioburden controlled, initial cleaning and sanitization (for example by contacting the flow path with sodium hydroxide solutions) or sterilization can be avoided. When using the SUT for a single run or batch only, even cleaning post-use may be omitted. With these features, SUT equipment provides improved efficiency, safety and convenience. However, regardless of using a pre-packed column for a single drug product only or for multiple drug products, there is typically a need to use the same column in multiple production runs, batches and production campaigns, primarily for reasons of cost. Thus, disconnecting and re-connecting the column to a chromatography system, or to different SUT flow paths of a chromatography system, that is providing and controlling the fluid flow over the column, is typically required in between said multiple production batches and/or production campaigns, and the column may be stored prior to re-connecting the column to the same or a different chromatography system or different flow paths. To allow for use of columns in multiple batches and production campaigns, these columns and/or the separation system(s) are often fitted with stainless steel valves at the interface of column and system to allow to close off the column during storage and to connect the column later to a chromatography system and use of the column for a subsequent production run. These stainless steel valves however require cleaning and sanitization and are costly when used for a single column and biopharmaceutical product only. SUMMARY An object of the invention is to provide a connection device for connecting a separation device to a separation system, such as for example a chromatography column to a chromatography system or to provide a separation device or a separation system comprising such a connection device which is facilitating easy connection, disconnection and/or, re-connection of device and system, and improving sanitization possibilities. A further object of the invention is to provide a connection device for connecting a separation device to a separation system or to provide a separation device or a separation system comprising such a connection device which is facilitating connection, disconnection and/or, re-connection of separation device and system, and facilitating removal of air in connections between the separation device and system without flushing air through the separation device, which is improving sanitization possibilities and efficiency in using the separation device and system. A further object of the invention is to provide a cost efficient connection device suitable for adaption to pre-packed chromatography columns and/or single-use chromatography columns as well as single-use systems which are used only for a limited number of drug products and/or production runs. This is achieved by a connection device and a separation device and a separation system according to the independent claims. According to one aspect of the invention a connection device is provided configured for connecting a separation system with a separation device, said connection device comprising: a separation device inlet connection configured for connection to a separa