US-12616920-B2 - Single-use device for the separation or filtering of a large volume of a mixture of substances

US12616920B2US 12616920 B2US12616920 B2US 12616920B2US-12616920-B2

Abstract

A single-use device for separating or purifying a large volume of a mixture of substances including membrane chromatography modules which are fixedly mounted in a predetermined grid and a line system for linking the membrane chromatography modules and for connecting the membrane chromatography modules to each other. A cover or bottom mechanism holding the membrane chromatography modules in position in a predetermined grid may be attached to the upper or lower side of the membrane chromatography modules. At least part of the line system is formed in the cover or the bottom mechanism, with connecting lines between the membrane chromatography modules. In a method of separating or purifying a large volume of a mixture of substances using such a single-use device having a plurality of automated valves and sensors connected to a control unit, the automated valves are controlled based on an evaluation of the parameters measured by the sensors.

Inventors

Thomas Loewe
Sebastian Handt
Stefan Schlack
Martin Leuthold

Assignees

SARTORIUS STEDIM BIOTECH GMBH

Dates

Publication Date: 20260505
Application Date: 20210204
Priority Date: 20200214

Claims (19)

1 . A single-use device for separating or purifying a volume of a mixture of substances, comprising a plurality of membrane chromatography modules which are fixedly mounted in a predetermined grid, and a line system for linking the membrane chromatography modules and for connecting the membrane chromatography modules to each other, wherein the membrane chromatography modules are characterized with regard to membrane adsorber, design and/or size, wherein the membrane chromatography modules and/or the line system are preconfigured for a desired process, and the membrane chromatography modules are upright in their position of use, further comprising a cover means and/or a bottom means attached to an upper side or a lower side, respectively, of the plurality of membrane chromatography modules and holding the membrane chromatography modules in position in the predetermined grid, wherein at least part of the line system of the single-use device is formed in the cover means and/or the bottom means, with connecting lines between the membrane chromatography modules, and wherein the cover means comprises individual, firmly interconnected segments, each of which is assigned to a membrane chromatography module.
2 . The single-use device according to claim 1 , characterized in that at least some of the membrane chromatography modules are configured as spiral-wound modules.
3 . The single-use device according to claim 1 , characterized in that the single-use device has at least two separate inlets which are assigned to different media.
4 . The single-use device according to claim 1 , characterized in that a prefilter is arranged upstream of at least one membrane chromatography module, the prefilter comprising a pleated filter element, and the prefilter having a pore size of about 0.45 μm.
5 . The single-use device according to claim 1 , characterized in that at least some of the lines of the line system are configured as rigid lines.
6 . The single-use device according to claim 1 , characterized in that the membrane chromatography modules are arranged such that starting from an inflow path, a flow to some or all of the modules is parallel.
7 . The single-use device according to claim 1 , characterized in that the membrane chromatography modules are arranged such that a flow to at least one group of modules is parallel to at least one further group of modules, while the flow to the modules within the groups is sequential.
8 . The single-use device according to claim 6 , characterized in that the flow paths through the membrane chromatography modules exposed to a parallel flow are each of equal length.
9 . The single-use device according to claim 1 , characterized in that the membrane chromatography modules are arranged such that a flow to all of them is sequential.
10 . The single-use device according to claim 1 , characterized in that automated valves, which are controlled by a control unit, are provided at a plurality of points in the lines of the line system.
11 . The single-use device according to claim 10 , characterized in that an additional inlet or outlet is provided at a point in the line system where a valve is arranged.
12 . The single-use device according to claim 10 , characterized by at least one single-use conductivity sensor and/or one single-use pH sensor and/or one single-use UV sensor, which is arranged upstream of an inlet and/or downstream of an outlet of one of the plurality of membrane chromatography modules or a group of the plurality of membrane chromatography modules linked by the line system.
13 . The single-use device according to claim 1 , characterized by at least one single-use pressure sensor and/or one single-use flow sensor arranged in one of the lines of the line system.
14 . The single-use device according to claim 12 , characterized in that the at least one sensor is connected to the control unit.
15 . The single-use device according to claim 1 , characterized in that the single-use device in an assembled state forms a closed and pre-sterilized unit, the membrane chromatography modules being already equilibrated in a buffer medium.
16 . The single-use device according to claim 1 , characterized in that the interconnected segments of the cover means include individually preconfigured or preconfigurable ports and line sections.
17 . The single-use device according to claim 1 , characterized in that at least one sensor or spectroscopic means is attached to an otherwise unused port of the cover means or the bottom means.
18 . A method of separating or purifying a volume of a mixture of substances, using a single-use device according to claim 1 , the single-use device comprising a plurality of automated valves and sensors, including at least one sensor selected from the group consisting of a single-use conductivity sensor, a single-use pH sensor, a single-use UV sensor, a single-use pressure sensor, or a single-use flow sensor, wherein the sensors are connected to a control unit, and the automated valves are being controlled based on an evaluation of operating parameters measured by the sensors.
19 . The method according to claim 18 , characterized in that signal threshold values are defined in advance for the operating parameters and in that, depending on an exceeding or dropping below the signal threshold values, predetermined process steps of the separation or purification are automatically carried out, including a valve switching sequence for collecting selected and separated fractions.

Description

FIELD OF THE INVENTION The invention relates to a single-use device for separating or purifying a large volume of a mixture of substances. BACKGROUND In the pharmaceutical production of high-quality active ingredients, single-use devices are generally used to an increasing extent due to the high flexibility achievable therewith, and due to the saving of time, investments and operating expenditure such as the cleaning, validation and examination of such ingredients. Single-use devices are increasingly desired for a larger scale (large volume production processes), wherein the costs for such systems should not rise to an unrealistic extent. WO 2017/032560 A1 shows a fully pre-sterilizable, ready-to-connect and integrity-testable single-use filtration device designed for large-volume filtration processes. This single-use filtration device comprises a plurality of single-use filter capsules of a standard size arranged in a predetermined grid and interconnected by lines. The filter capsules are supported by a rigid holder. A common air filter may be provided for venting the entire unit of the filter capsules. A preconfigured single-use filtration device is known from DE 10 2017 111 133 A1. The filtration device comprises a plurality of single-use filter capsules interconnected by rigid lines, which are firmly mounted in a universally predetermined grid by a rigid holder. In this filtration device, a pressure-stable sight glass is integrated into a vent line between a vent port and a sterile air filter provided for venting all filter capsules. The sight glass allows medium rising to the air filter to be made visible to the operator. As soon as the operator detects that water or other medium is rising to the air filter, he closes an associated vent valve in the line and takes further action if necessary. The known filtration devices can be integrated into a filtration train of a process arrangement by means of sterile connectors or hose welding, or in a non-sterile manner, for example by tri-clamp connections, and are thus “ready to use” after delivery to the user. Sterilization of the filtration devices even before delivery is possible. SUMMARY The object of the invention is to simplify the separation or purification of a large volume of a mixture of substances on the user-side and to make it safer by means of an optimized and flexible single-use device. This object is achieved by a single-use device having the features of claim 1. Advantageous and useful embodiments of the single-use device according to the invention are specified in the subclaims. The single-use device according to the invention for separating or purifying a large volume of a mixture of substances comprises a plurality of membrane chromatography modules which are fixedly mounted in a predetermined grid. The single-use device further comprises a line system for linking the membrane chromatography modules and for connecting the membrane chromatography modules to each other. The membrane chromatography modules, in particular with regard to membrane adsorber type, design and/or size, and/or the lines of the line system are preconfigured or adapted to be preconfigured for a desired process. With regard to the scope of application of the single-use device according to the invention, a distinction must be made between small media volumes, such as those used in the laboratory when developing a new process (laboratory scale), and large media volumes, which are implemented in production processes (production scale). Though a clear delimitation between small and large media volumes is not readily possible, the publication “Membranadsorber-Chromatographische Aufreinigung in neuen Dimensionen” by Stefan Fischer-Frühholz, GIT Labor-Fachzeitschrift June 2004, pages 603-605, GIT-Verlag GmbH & Co. KG, Darmstadt, available on the Internet at http://microsite.sartorius.com/en/biotechnology/laboratory/products_applications/membrane_adsorbers/literature/pdfs/Fischer-F_2004_MA_Aufreinigung_in_neuen_Dimensionen.pdf, gives some indications as to which ranges of substance mixture quantities or flow rates are more likely to be assigned to analysis and which ranges of quantities or flow rates are more likely to be assigned to production. In principle, however, quantities of less than one liter typically fall under laboratory scale, regardless of the specific field of application (vaccines, antibodies, etc.). The invention is based on the findings that, using suitable measures, large-volume membrane chromatography processes can be carried out in a simple and yet variable manner. Membrane chromatography is for polishing applications (removal in particular of viruses, DNA and host cell protein). Further typical applications include concentration, purification and desalting of peptides, flow-to-waste and analyte collection, protein purification and sample preparation. A more recent field of application is virus purification in vaccine production. Thin, synthetic, porous memb