Factors affecting the quality of therapeutic proteins in recombinant Chinese hamster ovary cell culture

Tae Kwang Ha, Dongil Kim, Che Lin Kim, Lise Marie Grav, Gyun Min Lee*

*Corresponding author for this work

Research output: Contribution to journalReviewpeer-review


Chinese hamster ovary (CHO) cells are the most widely used mammalian host cells for the commercial production of therapeutic proteins. Fed-batch culture is widely used to produce therapeutic proteins, including monoclonal antibodies, because of its operational simplicity and high product titer. Despite technical advances in the development of culture media and cell cultures, it is still challenging to maintain high productivity in fed-batch cultures while also ensuring good product quality. In this review, factors that affect the quality attributes of therapeutic proteins in recombinant CHO (rCHO) cell culture, such as glycosylation, charge variation, aggregation, and degradation, are summarized and categorized into three groups: culture environments, chemical additives, and host cell proteins accumulated in culture supernatants. Understanding the factors that influence the therapeutic protein quality in rCHO cell culture will facilitate the development of large-scale, high-yield fed-batch culture processes for the production of high-quality therapeutic proteins.

Original languageEnglish
Article number107831
JournalBiotechnology Advances
Number of pages16
Publication statusPublished - 2022

Bibliographical note

Funding Information:
This work was supported in part by the Samsung Research Funding Center of Samsung Electronics ( SRFC-MA1901-09 ) and the Novo Nordisk Foundation ( NNF10CC1016517 ).

Publisher Copyright:
© 2021 Elsevier Inc.


  • Chemical additive
  • CHO
  • Culture environment
  • Host cell protein
  • Mammalian cell culture
  • Quality attribute
  • Therapeutic protein


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