Development of a Single-Step Antibody-Drug Conjugate Purification Process with Membrane Chromatography.

Area of Science:

• Biotechnology
• Biopharmaceutical Manufacturing
• Chromatographic Techniques

Background:

• Membrane chromatography is standard for antibody purification, removing impurities like host cell proteins and aggregates.
• Its application in antibody-drug conjugate (ADC) purification is limited and typically confined to specialized uses.
• Developing efficient purification methods is crucial for ADC manufacturing.

Purpose of the Study:

• To evaluate the use of Sartobind® S and Phenyl membrane adsorbers for ADC purification.
• To assess the capability of these membranes for aggregate and payload clearance in a single chromatographic run.
• To establish an efficient and simplified purification scheme for ADCs.

Main Methods:

• Utilized Sartobind® S membrane for excess payload removal.
• Employed Sartobind® Phenyl membrane for polishing ADCs, clearing aggregates and specific drug-to-antibody ratio (DAR) species.
• Integrated both membranes in tandem for a single-run purification process.
• Optimized binding, washing, and elution conditions for the tandem system.

Main Results:

• Sartobind® S achieved log-fold clearance of free payload within a 10 membrane-volume wash.
• Sartobind® Phenyl reduced aggregates and higher DAR species, enhancing DAR homogeneity.
• The tandem membrane system simplified the process into a single chromatographic run.
• The optimized tandem approach reduced processing time and solvent consumption while maintaining high yield.

Conclusions:

• Tandem membrane chromatography using Sartobind® S and Phenyl offers an efficient purification strategy for ADCs.
• This method simplifies ADC downstream processing, reducing time and resource requirements.
• The system demonstrates potential for implementation in industrial-scale ADC manufacturing.