Effect of Cell Culture Process Change from Fed-batch to Continuous on Productivity and Product Quality

Integrated continuous bioprocessing has attracted a growing interest due to its potential to improve agility and flexibility in the manufacture of therapeutic proteins. To convert an existing fed-batch cell culture process to continuous, or perfusion, the major technical hurdles include maintaining steady state cell culture performance and generating a product with comparable product quality attributes. In this presentation, we evaluated three molecules including a fusion protein, an a glycosylated monoclonal antibody (mAb), and a glycosylated mAb. Steady state culture at high cell density was achieved for all three molecules, which allows the delivery of products with consistent product quality and adequate productivity. However, as compared to fed-batch processes, product quality and cell specific productivity differences were observed in perfusion cultures.  Further studies indicated that it was feasible to modulate product quality in perfusion process by adding process levers in culture medium. It was also feasible to increase cell specific productivity through medium and process optimization. This presentation provides an insight into the product quality and productivity differences between traditional fed-batch and perfusion cell culture processes and potential approaches to addressing these differences.
Presented by Ru Zang, Associate Director at Mersana Therapeutics

Ru Zang, Ph.D, is associate director of CMC at Mersana Therapeutics.  Prior to Mersana, she was a senior process engineer at Momenta Pharmaceuticals, where she led a group in establishing the continuous platform for process intensification. She has 6+ years’ experiences in biopharmaceutical industry and her expertise includes biologic process development, process characterization, scale-up and scale-down, tech transfer, GMP, project management and CMO management. Before Momenta, she was a scientist of Late Stage Process Development in Sanofi Genzyme. Dr Zang got her Ph.D degree in Chemical Engineering from The Ohio State University.
 
 
Sponsored by Repligen
Inspiring advances in bioprocessing, Repligen is a leader in bioprocess filtration, pre-packed chromatography and Protein A ligands development. Propelled by a culture of innovation and collaboration, and with a focus on cost and process efficiencies, our people and our technologies help meet critical bioproduction demands worldwide.  Named one of the fastest growing biotech companies in the USA, Repligen is headquartered in Boston, Massachusetts with major manufacturing sites in Massachusetts, California, Sweden, and Germany.
Products
Repligen offers the broadest range of hollow fiber and flat sheet filtration technologies for cell culture and purification, featuring XCell® ATF Systems, Spectrum® KrosFlo TFF Filters and Systems and TangenX® Flat Sheet TFF Cassettes.  As the expert in pre-packed chromatography technology, Repligen offers OPUS® Pre-packed Columns with unparalleled flexibility and scalability from bench- to production-scale. Since 1985, Protein A affinity ligands manufactured by Repligen have been routinely used to purify most of the world’s monoclonal antibodies.

Presented by John Bonham Carter, Product Line Lead, Cell Culture and Clarification Business at Repligen

John Bonham Carter is the Director of Upstream Sales at Repligen. John has been a serial entrepreneur with experience in multiple countries in industries from newspapers to biotechnology. Within bioprocessing, he has worked with many different upstream technologies and, most recently, has propelled the XCell™ ATF System to become the industry leader in continuous culture equipment supply. John is a regular international speaker on bioprocessing, SME entrepreneurship and business coaching. He is the editor of two eBooks: “Continuous Bioprocessing: Current Practice and Future Potential” and “Continuous Bioprocessing: Industry Best Practices”. John holds a Chemistry Degree from the University of Bristol.