Application of tangential flow-filtration (TFF) to enable solvent exchange and precipitation process for the production of payload-linkers of antibody-drug conjugates

Tangential Flow Filtration (TFF), also known as Crossflow Filtration, is a technique in which the fluid mixture flows tangentially (parallel) across the surface of the filter rather than being forced directly through it. This method is widely utilized in bioprocessing. We have demonstrated that TFF can be effectively applied in the enrichment process for the payload-linker prep HPLC purification, enabling significant volume reduction. The process works by allowing solvents to pass into the exchange buffer while retaining and concentrating the payload-linker product in the retentate. This approach facilitates solvent exchange, which in turn enables direct precipitation, eliminating the need for the time-consuming lyophilization step. The process has been successfully validated under GMP conditions at a production scale of 1 kg.