Continuous concentration and diafiltration tangential flow filtration with scalable dual membrane technology

Area of Science:

• Bioprocessing Engineering
• Membrane Filtration Technology
• Downstream Processing

Background:

• Continuous bioprocessing is crucial for efficient and economical biologics manufacturing.
• Tangential flow filtration (TFF), especially diafiltration, is a key downstream process.
• Existing TFF methods can be complex and may increase shear stress on valuable products.

Purpose of the Study:

• To present a novel flat sheet membrane cassette for single-pass TFF (SP-TFF) diafiltration.
• To enable efficient buffer exchange with optional simultaneous ultrafiltration.
• To reduce shear stress and process complexity in continuous biomanufacturing.

Main Methods:

• Development of a novel flat sheet membrane cassette for SP-TFF.
• Utilized bovine serum albumin (BSA) and real antibodies as model systems.
• Employed an automated lab-scale process system for data collection.
• Evaluated performance based on buffer exchange efficiency, transmembrane pressure (TMP), and permeate flux rates.

Main Results:

• Achieved ~97% to >99% buffer exchange at 3-7 diafiltration volumes with low TMP (50-350 mbar).
• Demonstrated comparable or reduced buffer consumption compared to conventional recirculation diafiltration.
• Observed permeability values of 10-60 L/(m²h) and feed flow rates of 1-7 L/(m²h).
• The system is scalable and suitable for closed, aseptic configurations.

Conclusions:

• The novel SP-TFF cassette effectively facilitates continuous diafiltration with high efficiency.
• This technology supports intensified and continuous biomanufacturing by simplifying downstream processing.
• The design offers reduced shear stress and operational complexity for biologics production.