Case study applied to the development of a Downstream Process (DSP)

This activity presents the standard steps of the Downstream (purification) process for monoclonal antibodies and cell therapies. It explores the main unit operations—chromatography, viral inactivation and filtration, diafiltration, and sterile filtration—their associated objectives (such as the removal of impurities like HCPs, DNA/RNA, and aggregates), as well as the specificities of the magnetic depletion process used for the selection of TCR(–) CAR(+) T cells.

This activity applies the Quality by Design (QbD) approach to the purification of monoclonal antibodies by identifying a Critical Quality Attribute (CQA)—the concentration of impurities (HCPs)—and analyzing the Critical Process Parameters (CPPs) associated with the polishing step. It guides the development of the Design Space using Design of Experiments (DoE), testing the effects of pH, ionic strength, and residence time on purification efficiency.

This activity details the purification process of CAR-T cells, with a focus on the removal of TCR(+) cells through magnetic depletion. It explores the key steps—labeling, incubation, and separation—identifies the Critical Process Parameters (CPPs), such as the volume of anti-TCR(+) antibodies and cell concentration, and demonstrates how to optimize these factors to maximize the purity of therapeutic TCR(–) CAR(+) cells.