Abstract

Mammalian cell culture medium development has widely evolved in recent years. The use of hydrolysates as serum replacement has led to process variability due to lot-to-lot variations. The undefined composition of these media could also increase the process optimization timelines, sometimes with limited impact on process performances. With the reduction of process development activities for preclinical and Phase I studies, medium and feed platforms raised. The objective of the media was to ensure cell growth only in order to go as fast as possible to production bioreactors while the feeds were responsible for productivity and production length. Either companies spent several months if not years to develop their own generic medium and feed platforms or they used commercial ones, sometimes under licenses. The medium and feed platform assessment also started earlier in the product development process. Clone screening was performed more and more in fed-batch conditions rather than batch ones. Thus screening tools, scale-down models of bioreactors, with lower and lower working volumes were designed. Another cell culture process evolution was the development of new expression systems without any selection agents. In order to assess our screening scale-down model, between 20 to 35 chemically defined platforms from 9 suppliers were screened with 3 CHO host cell lines/expression systems.

Highlights

  • Mammalian cell culture medium development has widely evolved in recent years

  • Fedbatch platform assessment was performed in 50 mL spin tubes at 37°C with a seeding density around 0.25 * 106 viable cells/mL

  • Despite having the same host cell, cell growth was different between mAb I and mAb II

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Summary

Introduction

Mammalian cell culture medium development has widely evolved in recent years. The use of hydrolysates as serum replacement has led to process variability due to lot-tolot variations. The objective of the media was to ensure cell growth only in order to go as fast as possible to production bioreactors while the feeds were responsible for productivity and production length. Either companies spent several months if not years to develop their own generic medium and feed platforms or they used commercial ones, sometimes under licenses. The medium and feed platform assessment started earlier in the product development process. Scale-down models of bioreactors, with lower and lower working volumes were designed. Another cell culture process evolution was the development of new expression systems without any selection agents. In order to assess our screening scale-down model, between 20 to 35 chemically defined platforms from 9 suppliers were screened with 3 CHO host cell lines/expression systems

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