Fedbatch culture and dynamic nutrient feeding

Katie F. Wlaschin, Wei Shou Hu

Research output: Contribution to journalArticlepeer-review

95 Scopus citations

Abstract

In the past decade, we have seen a rapid expansion in mammalian cell based therapeutic proteins reaching clinical applications. This increased demand has been met with much increased productivity through intensive process development. During this time, fedbatch culture processes have emerged as the predominant mode for producing recombinant proteins. In this review, we discuss the fundamentals of fedbatch culture process design, focusing on the use of stoichiometric nutrient requirements for feed medium formulation, and articulating the need and potential means for devising rational dynamic feeding schemes. Incorporation of on-line nutrient measurement will play a key role in further refinement of process control for the development of a much sought after generic feeding strategy that can respond to the changing demands of different cell lines in a fluctuating culture environment. The future of process engineering will likely require a combination of current process engineering strategies along with a better understanding and control over cell physiology. Process development will likely to entail not only optimizing traditional engineering parameters but also engineering cell lines with desired characteristics. The integration of cell engineering and process intensification will likely provide the stimuli that propel the limits of growth and productivity to the next high level.

Original languageEnglish (US)
Pages (from-to)43-74
Number of pages32
JournalAdvances in Biochemical Engineering/Biotechnology
Volume101
DOIs
StatePublished - Jun 8 2006

Keywords

  • Cell culture
  • Cell engineering
  • Metabolism
  • Process control
  • Process optimization

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

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