KR-20260065825-A - Eliminating bottlenecks in connected and/or high-titer fed-batch processes using low-concentration single-pass tangential flow filtration

Abstract

An exemplary system and method for receiving a feed flow at the feed flow inlet of a single-pass tangential flow filtration unit is provided, wherein the single-pass tangential flow filtration unit comprises one or more membranes or membrane devices in a one- or two-stage configuration, and the pressure drop across one or more membranes or membrane devices is 30 psi or less. The system and method are configured to use one or more membranes or membrane devices in a one- or two-stage configuration to separate a feed stream into a permeate stream and a residue stream, and to output the permeate stream through one or more permeate outlets and output the residue stream through one or more residue outlets.

Inventors

• 리엔, 몰리 카펜터
• 라짜레스키, 존 로버트
• 빌, 주니어, 제롬 조셉

Assignees

• 제넨테크, 인크.

Dates

Publication Date

20260511

Application Date

20240906

Priority Date

20230908

Claims (20)

1. A single-pass tangential flow filtration system comprising a single-pass tangential flow filtration unit configured to be fluidly connected to one or more preceding systems and one or more subsequent systems, wherein A single-pass tangential flow filtration unit comprises one or more membranes or membrane devices in a one-stage or two-stage configuration, and A single-pass tangential flow filtration system in which the pressure drop across one or more membranes or membrane devices is 30 psi or less.
2. A single-pass tangential flow filtration system according to claim 1, wherein the pressure drop across one or more membranes or membrane devices is less than 20 psi.
3. A single-pass tangential flow filtration system according to claim 1 or 2, wherein the single-pass tangential flow filtration unit is configured to be connected to one or more preceding systems by a supply flow inlet configured to receive a supply stream.
4. A single-pass tangential flow filtration system according to any one of claims 1 to 3, wherein the single-pass tangential flow filtration unit is configured to be connected to one or more subsequent systems by one or more residue flow outlets configured to output a residue stream.
5. A single-pass tangential flow filtration system positioned on a movable platform, in any one of paragraphs 1 to 4.
6. A single-pass tangential flow filtration system according to any one of claims 1 to 5, wherein a pump is not provided between the single-pass tangential flow filtration unit and one or more preceding systems.
7. A single-pass tangential flow filtration system according to any one of claims 4 to 6, further comprising a controller that communicates electrically with one or more sensors, wherein one or more sensors are provided in a supply line that is in fluid communication with a supply flow inlet, one or more permeate lines that are in fluid communication with one or more permeate outlets, and one or more residue lines that are in fluid communication with one or more residue outlets.
8. A single-pass tangential flow filtration system according to claim 7, wherein the controller is configured to control the volumetric concentration coefficient based on a determined volumetric concentration coefficient.
9. A single-pass tangential flow filtration system according to claim 8, wherein the volumetric concentration coefficient is determined based on the readings of a first sensor and a second sensor among one or more sensors.
10. A single-pass tangential flow filtration system according to claim 9, wherein the first sensor is a flow meter provided to a supply line fluidly communicating with a supply flow inlet, and the second sensor is a flow meter provided to a residue flow line of one or more residue flow lines fluidly communicating with one or more residue outlets.
11. A single-pass tangential flow filtration system, wherein, in claim 9 or 10, the volumetric concentration coefficient is determined based on the ratio of the measured flow rate of the feed stream to the measured flow rate of the residue stream, and each flow rate is measured by the first and second sensors.
12. A single-pass tangential flow filtration system, wherein the first sensor is a protein concentration sensor provided in a supply line fluidly communicating with a supply flow inlet, and the second sensor is a protein concentration sensor provided in a residue flow line of one or more residue flow lines fluidly communicating with one or more residue outlets, and the volumetric concentration coefficient is determined based on the ratio of the measured protein concentration of the residue stream to the measured protein concentration of the supply stream, and each protein concentration is measured by the first and second sensors.
13. In any one of paragraphs 8 to 12, controlling the volumetric concentration coefficient is: A single-pass tangential flow filtration system comprising adjusting the flow rate of a permeate stream to bring the volume concentration coefficient within the critical range, based on a determined volume concentration coefficient and determining that the volume concentration coefficient is outside the critical range.
14. A single-pass tangential flow filtration system according to Clause 13, wherein the critical range is 1.0 or greater and 3.0 or less.
15. A single-pass tangential flow filtration system according to claim 13 or 14, wherein the critical range is 1.5 or greater and 2.5 or less.
16. A single-pass tangential flow filtration system according to any one of claims 13 through 15, wherein adjusting the flow rate of the permeate stream to bring the volumetric concentration factor within a critical range comprises: activating or deactivating one or more permeate control pumps provided to one or more of one or more permeate lines downstream of one or more permeate outlets.
17. A single-pass tangential flow filtration system according to paragraph 16, wherein one or more of the permeate control pumps comprise one or more variable displacement pumps.
18. A single-pass tangential flow filtration system according to claim 17, wherein adjusting the flow rate of the permeate stream to bring the volumetric concentration coefficient within a critical range comprises increasing the displacement of one of one or more variable displacement pumps.
19. A single-pass tangential flow filtration system according to claim 17 or 18, wherein adjusting the flow rate of the permeate stream to bring the volumetric concentration coefficient within a critical range comprises reducing the displacement of one of the one or more variable displacement pumps.
20. A single-pass tangential flow filtration system according to any one of claims 16 to 19, wherein one or more of the permeate control pumps comprises one or more fixed displacement pumps.

Description

Eliminating bottlenecks in connected and/or high-titer fed-batch processes using low-concentration single-pass tangential flow filtration Cross-reference regarding related applications This application claims priority to U.S. Provisional Application No. 63/581,556 filed September 8, 2023, the entire contents of which are incorporated herein by reference. Field of invention The present disclosure relates to systems and methods for single-pass tangential flow filtration (SPTFF) in general, particularly to modular one-stage or two-stage SPTF configurations with low pressure drop across the system. SPTFF is based on conventional tangential flow filtration technology and is generally used to reduce the volume and increase the concentration of substances contained in liquids, such as protein solutions. Specifically, SPTFF is a filtration method that does not require recirculation, and it increases the concentration of protein solutions by removing buffer solution while maintaining the product as it flows through a semipermeable membrane. SPTFF has been shown to be effective in reducing process volume by 15 to 25 times using membranes configured in series, parallel, or both. The development of high-potency processes imposes constraints on manufacturing facilities as pool volumes increase to accommodate higher loading mass densities (for example, affinity chromatography requires more cycles to process the mass of high-potency cell culture processes, thus increasing pool volume). As a result, pool volumes may exceed the existing stainless steel tank sizes of the facility, potentially leading to facility compatibility issues. Additionally, processing large volumes in subsequent process steps results in longer run times, impacting plant productivity. Pool tank capacity may also be affected by the dilution and conditioning steps of a given process. Existing solutions to facility suitability constraints are often temporary, achieved by utilizing additional pool tanks at the affected process step(s) or by implementing SPTFF using existing Ultrafiltration-Tangential Flow Filtration/Tangential Flow Filtration (UFDF/TFF) skids combined with commonly available existing membranes. Furthermore, many currently available SPTFF solutions aim for high volumetric concentration factors exceeding 5.0, and the membrane area and configuration required to achieve these targets (typically at least 3-4 filter stages) result in high pressure drop across the filter membranes (e.g., exceeding 30 psi). As discussed overall, the volumetric concentration factor is a function of the feed flow rate and the residue flow rate. Furthermore, due to the magnitude of the pressure drop across the system under these operating conditions, it is often not possible to connect directly to a previous process step (e.g., a chromatography column) for continuous processing. Consequently, connection and continuous processing have been difficult due to the high target concentration factor of existing SPTFF solutions and the resulting high pressure drop. Therefore, to alleviate the manufacturing bottlenecks described above, there is a need for an SPTFF system and method that can be used as a modular ('plug and play') system. The SPTFF system and method described herein are configured to increase the protein solution concentration of a fluid by receiving a feed flow at one or more feed flow inlets/ports and directing the feed flow to one or more filter membranes configured to remove a buffer solution as the fluid passes through one or more semipermeable filter membranes while retaining the product. The removed buffer solution is described throughout as "permeate," and the product as "residue." As described, SPTFF systems are generally designed to achieve a volumetric concentration factor greater than 5.0, which is the ratio of residue protein concentration to feed protein concentration but can be approximated by the residue and feed flow rates, and to achieve such a high volumetric concentration factor, at least 3-4 filtration stages are generally required. On the other hand, since the system and method disclosed herein are designed for a low concentration factor (e.g., 1.0 to 5.0), only one or two filtration stages are required. In some embodiments, the SPTFF system disclosed herein may include a 3:2 filter membrane configuration (i.e., the system may include two filtration stages, wherein the first filter membrane has three membranes and the second filter membrane has two membranes), a 3:1 filter membrane configuration, or a 4:1 filter membrane configuration. A one- or two-stage configuration can reduce pressure drop across the entire system (from the feed flow inlet to the residue outlet or residue port) compared to a three- or four-stage configuration, providing a modular SPTFF system that can be connected to various preceding and subsequent processes as needed, and does not require a feed pump or pool tank at the outlet of the preceding process. That is, while