Researcher ORCID Identifier

Date Degree Awarded

Spring 5-13-2023

Degree Type

Open Access Dissertation

Degree Name

PHD in Applied Life Sciences

First Thesis/Dissertation Advisor

Hu Zhang

Second Thesis/Dissertation Advisor

Sue Behrens

Third Thesis/Dissertation Advisor

Raquel Orozco

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Current industrial practices for producing biopharmaceuticals include fed-batch production with batch isolation and purification. Nonproductive hold-up steps and manual offline measurements are common in batch processing which increases processing time and contributes to a high cost of production. Current market trends and cost pressures in the biopharmaceutical industry are creating a push to innovate bioprocessing platforms. Continuous bioprocessing has been considered a solution to the current limitations of batch production of biopharmaceuticals. Continuous bioprocessing involves intensifying individual processing steps by eliminating hold-up steps through a continuous operation to increase productivity, which results in advantages such as lower capital and production costs, higher equipment utilization efficiencies, smaller facility footprints, and increased manufacturing flexibility. Current bottlenecks of implementing continuous bioprocessing include technologies for real-time monitoring and control of critical/key process parameters and versatile scale-down models for process understanding and development. Commercially available platforms for implementing continuous bioprocessing are often expensive and inflexible. Technologies including Raman spectroscopy, perfusion cell culture, and continuous chromatography are explored in this Ph.D. study to develop a proof-of-concept, versatile bench-scale continuous platform driven by open-source software. Real-time, at-line monitoring of critical nutrients for cell culture via Raman spectroscopy allows for providing feedback control to nutrient pumps to maintain a continuous supply of these nutrients to cells for the production of biopharmaceuticals, and the products are continuously harvested in a perfusion process to a two-column platform for protein A capture. The preliminary data supports that the bench-scale platform is readily maneuverable to customized requirements, adaptable for the production of different modalities, and much cheaper for implementation.

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© 2023 Christine Urrea