Resins Address Downstream Purification Concerns

What It Covers

Avantor's Dr. Jared Brophy examines downstream biopharmaceutical purification bottlenecks, focusing on chromatography resins, mixed-mode technologies, buffer optimization, and digital analytics tools. Downstream processing accounts for roughly 60% of total biologics production effort, with up to 30% of harvested material lost across multiple purification steps.

Key Questions Answered

• •Downstream bottleneck scale: Downstream purification represents approximately 60% of total biologics production effort, yet has not kept pace with upstream gains. Upstream titers have risen from milligrams to 4–6 grams per liter, while downstream losses reach up to 30% of harvested material — making this the highest-leverage area for yield and cost improvement.
• •Mixed-mode chromatography consolidation: Mixed-mode and multimode resins use ligands with two or more simultaneous interaction mechanisms, enabling a single resin to replace multiple sequential chromatographic columns. By modulating the mobile phase rather than switching resins, manufacturers can merge two purification steps into one, directly reducing processing time, material costs, and yield losses per gram of drug.
• •Universal buffer strategy: Moving from single-purpose pH-targeted buffers to universal buffers usable across multiple process steps reduces the number of materials to acquire, store, and manage. Pairing this with prequalified, single-use buffer concentrates that plug directly into workflows — plus selective hydrophobicity-modulating additives — improves impurity clearance, column performance, and overall cost per gram.
• •Chromatography digital twins: Chromatography is well-suited for digital twin modeling because its underlying physics and biochemistry are well characterized. Manufacturers should integrate process data, stability data, and certificate-of-analysis variables to detect raw material variability that passes specifications but still affects yields — enabling tighter input controls and proactive process corrections before batch failures occur.
• •Affinity chromatography ligand evolution: Protein A remains the dominant and most costly capture step for monoclonal antibody purification. As biologics diversify into bispecifics, ADCs, Fab fragments, and FC fusion proteins, manufacturers should evaluate Protein L and novel Protein A presentations tailored to these formats, while using mobile-phase additives to improve affinity step efficiency and reduce cost per gram.