Automation and Control of a Precipitation-based Continuous Downstream Process for High Titer Products

A proposal to commercialize a continuous downstream process for monoclonal antibody production using precipitation and flowthrough chromatography. It aims to cut costs and boost sustainability. Led by RPI with top academic and industry partners.

Industry Need

The biopharmaceutical industry urgently needs a more sustainable, cost-effective, and scalable downstream process for monoclonal antibody (mAb) production. Current protein A-based platforms are expensive, buffer-intensive, and unable to meet rising global demand—especially in low- and middle-income countries. A fully continuous, precipitation-based process offers a transformative solution by reducing costs, increasing throughput, and improving environmental sustainability, while maintaining product quality.

Approach

The project meets industry needs by developing a fully continuous, precipitation-based downstream process for monoclonal antibody production. It replaces costly, unsustainable protein A methods with a scalable, automated system that improves yield, reduces buffer use, and enhances environmental and economic sustainability. The project builds upon the successes of PC4.1-105 and involves a three-part strategy: Instrumentation and Automation, Supervisory Control and Optimization, and Commercial Scale-up.

Impacts

Fully continuous precipitation-based downstream process, instrumentation, and control system available for tech transfer to a testbed or member lab.

Reduced COGs, supply chain complexity, and capacity bottlenecks with continuous precipitation for downstream capture as an alternative to ProA resin.

Increased flexibility and resilience with option to uncouple manufacturing process at the capture-polish operation interface with concentrated target protein hold and later polish, formulation, and fill.