(523f) Development of a Multi-Column Continuous Chromatography Process for Antibody Drug Conjugates

Column chromatography is often a key enabling purification unit operation in the development of antibody-drug conjugates (ADCs) and associated drug linkers, essential to obtain a product that meets regulatory requirements. Column chromatography processes developed for ADCs and drug linkers have been in batch mode to date which limits the throughput and yield. On the other hand, continuous chromatography is well-known to improve productivity and throughput in biologic downstream processing. To meet the increased ADCs demand, developing expertise in continuous chromatography becomes crucial. Different designs have been investigated for continuous chromatography systems with varying column counts, configurations, and modes of operation such as three-column periodic counter-current chromatography (PCC), simulated moving bed (SMB), and sequential multicolumn chromatography with recycling. In this presentation, we have explored the twin-column recycling continuous chromatography, otherwise known as MCSGP (Multi-Column Solvent Gradient Purification) for developing continuous chromatography for ADC purification. Unlike single-column chromatography, there is no trade-off between yield and purity in continuous chromatography and the product waste from the crude material is minimized. Furthermore, continuous chromatography reduces solvent and buffer consumption while increasing yield and purity. Here we will present a comparison of the throughput, yield, and buffer consumption for the batch and MCSGP processes.