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:
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:
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
Implementing the fully continuous downstream process developed under PC4.1-105 can reduce buffer usage by up to 70% and increase throughput by 60%, translating into significant cost-of-goods savings. This positions manufacturers to meet global demand more efficiently and at lower cost.
Development and demonstration of a new fully continuous downstream purification process for monoclonal antibodies (mAbs), replacing Protein A chromatography with precipitation-based capture and flow-through polishing steps.
Bench-scale and pilot-scale system implementation, including integration of precipitation, dewatering, washing, redissolution, and polishing operations using commercial hardware (e.g., ChromaTan CCTC Mini system).
Screening protocols and optimized operating conditions for precipitation, washing, and polishing steps, including resin selection and flow-through conditions for activated carbon and multimodal anion exchange resins.
Minervini, M., Mergy, M., Zhu, Y., Gutierrez Diaz, M. A., Pointer, C., Shinkazh, O., Oppenheim, S. F., Cramer, S. M., Przybycien, T. M., & Zydney, A. L. (2023). Continuous precipitation-filtration process for initial capture of a monoclonal antibody product using a four-stage countercurrent hollow fiber membrane washing step. Biotechnology and Bioengineering. https://doi.org/10.1002/bit.28525
Azzariti, L., Minervini, M., & Behboudi, A., Development of a microfiltration process for the purification of precipitated monoclonal antibodies and precipitated proteins, American Institute of Chemical Engineers Fall National Meeting, Orlando, FL, November 7, 2023.
Mergy, M., Ghosh, S., Minervini, M., Bequette, W., Zydney, A., Cramer, S., & Przybycien, T., Feedback Control of Particle Morphology Enables Continuous Monoclonal Antibody Capture via Precipitation, Integrated Continuous Biomanufacturing V, Sitges, Spain, October 10, 2022.
Mergy, M., Minervini, M., Gutierrez, M., Cramer, S., Zydney, A., & Przybycien, T. M., Improving the performance of a fully continuous monoclonal antibody purification processing with capture via precipitation, American Chemical Society Fall 2023 National Meeting, San Francisco, CA, August 16, 2023.
Minervini, M. & Zydney, A., Effect of Membrane Module Geometry on the Critical Flux for IgG Precipitates, American Institute of Chemical Engineers Fall National Meeting, Phoenix, AZ, November 17, 2022.
Minervini, M., Mergy, M., Gutierrez, M., Zhu, Y., Shinkazh, O, Pointer, C., Cramer, S., Przybycien, T., & Zydney, A., Continuous precipitation-filtration process for initial capture of a monoclonal antibody product using a four-stage countercurrent hollow fiber membrane washing step, American Chemical Society Fall National Meeting, San Francisco, CA, August 14, 2023.
Przybycien, T. M., A Fully Continuous Downstream Process for mAb Manufacture, 2022 NIIMBL National Meeting, Washington, DC, July 28, 2022.
Przybycien, T. M., Zydney, A., Cramer, S., & Bequette, W., A Fully Continuous and Modular Monoclonal Antibody Purification Process with Capture via Precipitation, Integrated Continuous Biomanufacturing V, Barcelona, Spain, October 10, 2022.
Przybycien, T. M., Zydney, A., Cramer, S., & Bequette, W., A Fully Continuous and Modular Monoclonal Antibody Purification Process with Capture via Precipitation, Integrated Continuous Biomanufacturing V, Sitges, Spain, October 10, 2022.
Shinkazh, O., Bequette, W., Cramer, S., Przybycien, T. M., & Zydney, A., Implementation and “Platformization” of a Fully Continuous, Precipitation-based Downstream Process for mAb Manufacture, 2023 NIIMBL National Meeting, Washington, DC, June 29, 2023.
Zydney, A., Continuous biomanufacturing: A new paradigm for production of monoclonal antibodies, Advances in Drug Discovery and Development – Online Symposium, Virtual, October 26, 2022.
Zydney, A., Continuous biomanufacturing: New opportunities for membrane technology, 2nd Greater Bay Area Symposium on Separation and Purification Technology, Virtual, May 19, 2023.
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Rensselaer Polytechnic Institute
AstraZeneca
ChromaTan Corporation
EMD Millipore Corporation
Janssen Research & Development, LLC
Merck Sharp & Dohme LLC
Takeda Pharmaceuticals
The Pennsylvania State University
