Finding ways to remove bottlenecks and improve yields in downstream processing for monoclonal antibodies (mAbs) continues to be a key focus area for biopharma manufacturers. In downstream processing, the goal is to improve recovery and reduce the cost per gram of protein produced. Nandu Deorkar, Jungmin Oh, Pranav Vengsarkar and Jonathan Fura at Avantor focus on areas where streamlining downstream processing steps can help improve overall mAbs processing efficiencies and help downstream productivity match the improved efficiencies achieved in upstream processing.
Maximising mAbs Purification Efficiency: Focus Areas for Reducing Bottlenecks in Downstream Processing
When compared to upstream processing, finding efficiencies and economies of scale in downstream steps involves more complex analysis and optimisation. Significant investments have already been made in the technologies and processes used in upstream processes. Improvements to raw material characterisation and the addition of single-use systems, perfusion systems and more precisely controlled bioreactors in upstream processing steps are all leading to measurable increases in upstream yields. However, improvements in downstream throughput have not kept a similar pace to those for upstream, leading to potential bottlenecks in the end-to-end process.
Expanding the use of mixed-mode and multimode chromatography resins – using resins to target ligands for increased selectivity can help to process targeted molecules more efficiently – and exploring ways to make chromatography buffers more effective – using new kinds of additives and prepackaged single-use buffer materials to streamline buffer preparation steps – are two potential areas for optimisation that could lead to significant downstream improvement.
How Resin Choice Impacts Overall Operations
Downstream processing generally takes place over a period of a few weeks. Multiple chromatographic steps, filtration steps, buffers and cleaning solutions are used as part of the process. A capture step is the first purification step where protein A has become the most widely used resin due to its highly specific nature, ease of use as a standard purification process and proven regulatory record. The protein A step is one area where process efficiencies and cost savings may be gained by selecting a high-performance protein A resin and optimising buffer preparation.
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