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A Fully Continuous Downstream Process for High Titer Products

Prepare a new intensified, continuous purification process for antibodies by eliminating “Protein A” affinity chromatography, by employing precipitation capture purification, tangential flow filtration, and flow-through chromatography for polishing.
Categories
Drug substance
Project status
100% Completed

Industry Need

  • New purification processes are required to meet the global need for high-purity, high-volume, high-dose protein therapeutics. 
  • Monoclonal antibodies (mAbs) to treat pandemic infection, high cholesterol, and Alzheimer’s disease are at the forefront of this need. 
  • “Protein A” affinity chromatography is the bottleneck of the current “platform” mAb manufacturing process.


Solution

The team developed a new type of intensified, continuous purification process that can meet the industry need by eliminating “Protein A” affinity chromatography, the bottleneck of the current “platform” mAb manufacturing process.  

This new process employs: 

  • Precipitation for capture purification 
  • Tangential flow filtration for concentration and washing 
  • Flow-through chromatography for polishing 

The process can be operated in an integrated, fully continuous mode, increasing volumetric throughput while reducing buffer usage, cost-of-goods, and equipment and supply chain performance bottlenecks of Protein A-based mAb processing that limit global manufacturing capabilities.  

Project steps included: 

  • Screening up to 10 different crude mAbs from biomanufacturing partners to determine suitability and conditions for the new process, with up to 5 of the best-suited mAbs purified in the integrated process at bench-scale in extended time demonstration runs.  
  • Transferring the precipitation-based capture technology to integrated pilot-scale equipment for further extended performance testing using 2 mAbs from the bench-scale demonstration. 


Outcomes and Impacts

Will provide results needed to facilitate widespread industry adoption of this new process.

Will enable de-risking of an innovative recombinant protein purification process that is based on non-traditional continuous precipitation and flowthrough chromatography purification operations

Will offer relief from the capacity, buffer usage, cost, and supply chain bottlenecks of the current "platform" purification process for antibodies

Will reduce process and supply chain complexity rendering process suitable for global deployment, including low-resource environments

Updates, Related Publications, and Deliverables

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Project Lead

Rensselaer Polytechnic Institute

Rensselaer Polytechnic Institute

Participating Organizations

AstraZeneca

AstraZeneca

ChromaTan Corporation

ChromaTan Corporation

Janssen Research & Development, LLC

Janssen Research & Development, LLC

Merck Sharp & Dohme LLC

Merck Sharp & Dohme LLC

MilliporeSigma/EMD Serono

MilliporeSigma/EMD Serono

Takeda Pharmaceuticals

Takeda Pharmaceuticals

The Pennsylvania State University

The Pennsylvania State University