US-12616919-B2 - Optimizing the operation of a chromatography system

US12616919B2US 12616919 B2US12616919 B2US 12616919B2US-12616919-B2

Abstract

The present invention relates to a method for purifying a feed comprising at least one target product in a chromatography system having a plurality of purifying units, each having an inlet and an outlet, and a valve assembly having an outlet port and an inlet port. The inlet and the outlet of each purifying unit being connected to a respective port of the valve assembly. The method comprising loading (S 10 ) the plurality of purifying units with feed provided through the inlet port of the valve assembly by sequentially connecting each purifying unit to the inlet port of the valve assembly: eluting (S 12 ) the plurality of purifying units using an elution provided through the inlet port of the valve assembly by sequentially connecting each purifying unit to the inlet port of the valve assembly: and collecting (S 14 ) the at least one target product from the outlet port of the valve.

Inventors

Matthew Townsend
Ian Scanlon

Assignees

CYTIVA SWEDEN AB

Dates

Publication Date: 20260505
Application Date: 20200224
Priority Date: 20190228

Claims (10)

1 . A method for purifying a feed comprising at least one target product in a chromatography system having a plurality of adsorption purifying units, each purifying unit having an inlet and an outlet, and a valve assembly comprising a single rotary valve, an outlet port, and an inlet port, wherein the inlet and the outlet of each purifying unit is connected to a respective port of the valve assembly, said method comprising: a) loading the plurality of purifying units with feed provided through the inlet port of the valve assembly by sequentially connecting each purifying unit to the inlet port of the valve assembly; b) when step a) is completed, eluting the plurality of purifying units using a solution to elute provided through the inlet port of the valve assembly by sequentially connecting each purifying unit to the inlet port of the valve assembly; and c) collecting the at least one target product from the outlet port of the valve assembly; wherein the loading step is performed for each of the plurality of purifying units, then the eluting step is performed for each of the plurality of purifying units, and then the collecting step is performed for each of the plurality of purifying units, such that the purification of the feed is a semi-continuous process; wherein each purifying unit of the chromatography system is a membrane adsorber; and wherein the plurality of purifying units are connected in parallel.
2 . The method according to claim 1 , wherein the membrane adsorber comprises electrospun material.
3 . The method according to claim 1 , wherein each purifying unit is selected to be a column comprising the membrane adsorber.
4 . The method according to claim 1 , wherein the chromatography system is further provided with a pretreatment device to the inlet of the valve assembly, and the method further comprises conditioning the feed before entering the inlet of the valve assembly.
5 . The method according to claim 4 , wherein the pre-treatment device is selected to be a filter or chromatography column configured to condition the feed by removing selected material.
6 . The method according to claim 1 , wherein the method further comprises when step b) is completed, washing the plurality of purifying units using a solution provided through the inlet port of the valve assembly by sequentially connecting each purifying unit to the inlet port of the valve assembly.
7 . The method according to claim 1 , wherein step b) further comprises, before eluting the plurality of purifying units, washing the plurality of purifying units using a solution provided through the inlet port of the valve assembly by sequentially connecting each purifying unit to the inlet port of the valve assembly.
8 . The method according to claim 1 , wherein steps a)-c) are repeated at least twenty times and during each repeated cycle a part of the same feed is purified using the same purifying units.
9 . The method according to claim 1 , wherein the purifying units are selected to be of the same type.
10 . A chromatography system for purifying a feed comprising at least one target product having a plurality of purifying units, each purifying unit having an inlet and an outlet, and a valve assembly comprising a single rotary valve, an outlet port, and an inlet port, wherein the inlet and the outlet of each purifying unit being connected to a respective port of the valve assembly, said chromatography system further comprises a control unit configured to: a) load the plurality of purifying units with feed provided through the inlet port of the valve assembly by sequentially connecting each purifying unit to the inlet port of the valve assembly; b) when step a) completed, elute the plurality of purifying units using a solution to elute provided through the inlet port of the valve assembly by sequentially connecting each purifying unit to the inlet port of the valve assembly; and c) collect the at least one target product from the outlet port of the valve assembly; wherein the loading step is performed for each of the plurality of purifying units, then the eluting step is performed for each of the plurality of purifying units, and then the collecting step is performed for each of the plurality of purifying units, such that the purification of the feed is a semi-continuous process; wherein each purifying unit of the chromatography system is a membrane adsorber; and wherein the plurality of purifying units are connected in parallel.

Description

CROSS REFERENCE TO RELATED APPLICATIONS This application claims the priority benefit of PCT/EP2020/054748, filed on Feb. 24, 2020, which claims the benefit of Great Britain Application No. 1902743.2, filed 28 Feb. 2019, the entire contents of which are incorporated by reference herein. FIELD OF THE INVENTION The present invention relates to optimizing operation of a chromatography system using a valve assembly for purifying a feed comprising at least one target product in a chromatography system having a plurality of purifying units. BACKGROUND OF THE INVENTION Physical separation methods in which the material separation occurs through distribution between a stationary phase and a mobile phase are known by the term chromatography. Examples of such chromatography methods are gel-permeation chromatography (GPC), adsorption chromatography, affinity chromatography, ion-exchange chromatography and hydrophobic interaction chromatography. In gel-permeation chromatography, the separation columns are usually filled with beads of a porous, highly cross-linked material. Conducted through this material is a fluid which comprises substances of differing molecular size. Substances of smaller molecular size, i.e. having a smaller hydrodynamic volume, diffuse into the solvent interface or into the pores of the gel and remain there until they diffuse back out of the solvent interface or the pores. The fractionation occurs because the larger molecules are exclude from part of the pore volume, i.e. spend less time in the stagnate volume inside the pores. Large solutes elute first. Gel-permeation chromatography is therefore a separation method which is commonly used both in chemical and in pharmaceutical development and production, more particularly for the isolation of biomolecules from complex mixtures which, for example, arise during the production of proteins in microorganisms or during the isolation of individual constituents from biological fluids, such as blood. In (membrane) adsorption chromatography, in contrast to gel-permeation chromatography, there is binding of components of a fluid, for example individual molecules, associates or particles, to the surface of a solid in contact with the fluid. A solid capable of adsorption is called an “adsorbent”, and the component to be adsorbed is called an “adsorbate”. Adsorption can be used industrially for adsorptive material separation, which is carried out in apparatuses called “adsorbers”. The adsorbate is referred to as a “target product” when its recovery from the fluid is intended, and as a “impurity” when it is to be removed from said fluid. In the first case, the adsorption has to be reversible, and the adsorption is followed, as a second step of the method, under modified conditions (composition and/or temperature) of the fluid, by the elution of the adsorbate. A target substance can be present as a single component in the fluid, and so the material separation is merely an enrichment, or there are multiple components which are to be separated. In this case, at least one of the steps of the method has to be selective, i.e. has to be achieved to different extents for the components to be separated. An example of a membrane adsorption material is described in WO 2018/037244, which is hereby incorporated by reference. U.S. Pat. No. 9,802,979, US2016/0288089, WO2018/0372444 and WO2018/011600 which are incorporated by reference, describes chromatography medium comprising one or more electrospun polymer nanofibres which form a stationary phase. Another example is Sartobind®, available from Sartorius. In a conventional liquid Chromatography system, such as the ÄKTA™ pure system (29-0211-96 AE) from GE Healthcare, valves are used in order to switch between the different modes of operation: load, wash and elute. When switching between modes of operation, valves and piping may contain residues from the previous step, which requires cleaning and increased usage of buffer solution. SUMMARY OF THE INVENTION An object of the invention is to provide an improved process to eliminate or at least reduce the above identified drawbacks. This object is achieved by a method for purifying a feed comprising at least one target product in a chromatography system having a plurality of purifying units, each purifying unit having an inlet and an outlet, and a valve assembly (40; 12) having an outlet port and an inlet port. The inlet and the outlet of each purifying unit is connected to a respective port of the valve assembly. The method comprises: loading the plurality of purifying units with feed provided through the inlet port of the valve assembly by sequentially connecting each purifying unit to the inlet port of the valve assembly; when loading is completed for all purifying units, eluting the plurality of purifying units using a solution to elute provided through the inlet port of the valve assembly by sequentially connecting each purifying unit to the inlet port of the valve assembly; an