Re-Imagining Chromatography: Building Efficient, Connected Downstream Processes

By Priyanka Gupta, Katy McLaughlin, Ganesh Kumar, and Sanket Jadhav

Process intensification strategies represent an excellent opportunity for improving overall efficiency within the biopharmaceutical industry. Significant progress toward process intensification has been made for well-established modalities such as monoclonal antibodies (mAbs), fusion proteins, and bi- and multi-specifics. The industry is also beginning to explore process intensification in newer modalities such as adeno-associated viruses (AAVs).

Most of these advances and process adaptations have been applied upstream, where the industry has many options for adopting intensification, from simple (N-1) perfusion to a steady-state perfusion process in the production (N) bioreactor. However, downstream processes have not kept up with these advances, so while upstream process intensification strategies have greatly improved productivity, the industry faces bottlenecks when purifying the feeds with increased titers.

Performing multiple downstream steps in parallel and in a connected process is a powerful approach to intensify existing and new platforms irrespective of the intensification status and readiness of the upstream process.

The case study shows a stepwise approach for integrating process intensification principles into an existing process to increase productivity, reduce costs, and improve process sustainability. The insights derived from this case study offer a tangible example of the application of process intensification principles in a downstream process.