Industrial Production of Therapeutic Proteins: Cell Lines, Cell Culture, and Purification



The biotechnology and pharmaceutical industries have seen a recent surge in the development of biological drug products manufactured from engineered mammalian cell lines. Since the hugely successful launch of human tissue plasminogen activator in 1987 and erythropoietin in 1988, the biopharmaceutical market has grown immensely. Global sales in 2003 exceeded US $30 billion [1]. Currently, a total of 108 biotherapeutics are approved and available to patients (Table 32.1). In addition, 324 medically related, biotechnology-derived medicines for nearly 150 diseases are in clinical trials or under review by the US Food and Drug Administration [2]. These biopharmaceutical candidates promise to bring more and better treatments to patients. Compared to small molecule drugs, biotherapeutics show exquisite specificity with fewer off-target interactions and improved safety profiles. Protein engineering technologies have advanced to create protein drugs with improved efficacy, specificity, stability, pharmacokinetics, and solubility. Strategies that have been employed to implement these changes include mutagenesis, recombination, and other directed evolution methods, as well as rational design and structure-based computational approaches [3–7]. These advanced protein engineering technologies are creating novel drug designs and clever treatment strategies that are fuelling the biopharmaceutical market growth.


Therapeutic Protein Mammalian Cell Culture Perfusion Culture Product Titer Host Cell Protein 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors would like thank all the colleagues who helped in many invaluable ways in the production of this chapter, in particular, Marie Ary, Kenton Abel, Bassil Dahiyat, Joyce Morrison, and Christopher O’Brien.


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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Marie M. Zhu
    • 1
  • Michael Mollet
    • 1
    • 2
  • Rene S. Hubert
    • 1
  1. 1.Technical Operations, Xencor Inc.MonroviaUSA
  2. 2.Process Development, Medimmune Inc.GaithersburgUSA

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