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Commercial production of recombinant erythropoietins

  • Alice S. Chuck
  • Adrian Distler
  • Shane A. Sander
  • Rohini R. Deshpande
  • Gregg Nyberg
  • James E. Seely
Part of the Milestones in Drug Therapy book series (MDT)

Abstract

For the production of recombinant products from genetically engineered cells, a number of cell hosts may be used, but they generally belong to one of five categories: plant, bacterial, yeast, insect, or mammalian. Depending on the type of product that is desired, the features of that product, the intended use of the product, and the preferred method of manufacture, an appropriate host cell can be selected. With the appropriate genetic engineering, the gene of interest such as erythropoietin (EPO) can be produced by a host cell. In the case of EPO production, the sequence of amino acids, as well as the amount of glycosylation, must be correct to achieve the desired efficacy in vivo. This chapter describes one method of EPO production using cells genetically engineered to secrete recombinant human erythropoietin (rHuEPO). In this method of production, mammalian cells, which are capable of producing glycosylation forms with the desired efficacy in humans, are typically selected as hosts. The host mammalian cells secrete the rHuEPO product into the medium environment in which they are cultured, making the remainder of production a matter of separating the rHuEPO product from the cells and other components in the cell culture broth. This chapter summarizes the generation of rHuEPO-producing cell lines, the production of rHuEPO, the separation of rHuEPO from components of the cell culture broth, and the packaging of the final rHuEPO drug product.

Keywords

Cell Bank Production Cell Line Recombinant Erythropoietin Roller Bottle Cell Culture Process 
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.

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References

  1. 1.
    Center for Biologies Evaluation and Research (CBER) and Center for Drug Evaluation and Research (CDER), Guidance for industry for the submission of chemistry, manufacturing, and controls information for a therapeutic recombinant DNA-derived product or a monoclonal, antibody product for in vivo use. 1996.Google Scholar
  2. 2.
    International Conference on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use. Q5D. 1997.Google Scholar
  3. 3.
    International Conference, on Harmonisation (ICH) of Technical Requirements for Registration of Pharmaceuticals for Human Use Q5A(R1) Viral Safety Evaluation of Biotechnology Products Derived From Cell Lines of Human or Animal Origin 1999.Google Scholar
  4. 4.
    Freshney RI. Culture of animal cells. Alan R Liss Inc, New York; 1983.Google Scholar
  5. 5.
    Ozturk SS. Engineering challenges in high density culture systems. Cytotechnol 1996;22:3–16.CrossRefGoogle Scholar
  6. 6.
    Chu L, Robinson DK. Industrial choices for protein production by large-scale cell culture. Curr Opin Biotechnol 2001;12:180–187PubMedCrossRefGoogle Scholar
  7. 7.
    Monroe RS, Huber BE. The major form of murine asialoglycoprotein receptor — cDNA sequence and expression in liver, testis and epididymus. Gene 1994;148:237–244PubMedCrossRefGoogle Scholar
  8. 8.
    Center for Drug Evaluation and Research. Q7A Good manufacturing practice guidance for active pharmaceutical ingredients. 2001.Google Scholar

Copyright information

© Birkhäuser Verlag/Switzerland 2009

Authors and Affiliations

  • Alice S. Chuck
    • 1
  • Adrian Distler
    • 2
  • Shane A. Sander
    • 2
  • Rohini R. Deshpande
    • 2
  • Gregg Nyberg
    • 3
  • James E. Seely
    • 3
  1. 1.Seattle GeneticsBothellUSA
  2. 2.Amgen Inc.Thousand OaksUSA
  3. 3.Amgen Inc.LongmontUSA

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