Advertisement

An Introduction to „Recent Trends in the Biotechnology Industry: Development and Manufacturing of Recombinant Antibodies and Proteins“

  • Michael Pohlscheidt
  • Robert Kiss
  • Uwe Gottschalk
Chapter
Part of the Advances in Biochemical Engineering/Biotechnology book series (ABE, volume 165)

Abstract

The production of the first therapeutic proteins in the early 1980s heralded the launch of the biopharmaceuticals industry. The number of approved products has grown year on year over the past three decades to now represent a significant share of the entire pharmaceuticals market. More than 200 therapeutic proteins have been approved, approximately a quarter of which are represented by monoclonal antibodies and their derivatives. In 2016, the list of the top 15 best-selling drugs included more than eight biologics and in 2020 the trend will continue, with more than 50% of the top 20 best-selling drugs predicted to be biologics. From 1986 to 2014 several first-in-class, advance-in-class, and breakthrough designated therapeutic options were approved, with advanced therapies such as immuno-oncology and cell-based therapies being approved for several indications.

Keywords

Antibody formats and evolution Biotechnology Cell culture PAT Processing technologies QbD 

References

  1. 1.
    Reichert JM (2001) Monoclonal antibodies in the clinic. Nat Biotechnol 19:819–822CrossRefGoogle Scholar
  2. 2.
    Reichert JM, Pavolu A (2004) Monoclonal antibodies market. Nat Rev Drug Discov 3:383–384CrossRefGoogle Scholar
  3. 3.
    Drapeau M, Sullivan F, Moniz Carpenter J (2007) Special report: blockbuster then and now–trends for billion-dollar drugs. Spectr Ther Markets Emerg Technol 12:1–39Google Scholar
  4. 4.
    Munos B (2009) Lessons from 60 years of pharmaceutical innovation. Nat Rev 8:959–968Google Scholar
  5. 5.
    Doig AR, Ecker DM, Ransohoff TC (2015) Monoclonal antibody targets and indications. Am Pharm Rev 15:177490Google Scholar
  6. 6.
    Ecker DM, Dana Jones S, Levine HL (2015) The therapeutic monoclonal antibody market. MAbs 7:9–14CrossRefGoogle Scholar
  7. 7.
    Choi JH, Lee SY (2004) Secretory and extracellular production of recombinant proteins using Escherichia coli. Appl Microbiol Biotechnol 64(5):625–635CrossRefGoogle Scholar
  8. 8.
    Baneyx F, Mujacic M (2004) Recombinant protein folding and misfolding in Escherichia coli. Nat Biotechnol 22(11):1399–1408CrossRefGoogle Scholar
  9. 9.
    Wurm FM (2004) Production of recombinant protein therapeutics in cultivated mammalian cells. Nat Biotechnol 22:1393–1398CrossRefGoogle Scholar
  10. 10.
    Sethuramann N, Stadheim TA (2006) Challenges in therapeutic glycoprotein production. Curr Opin Biotechnol 17(4):341–346CrossRefGoogle Scholar
  11. 11.
    Heath C, Kiss R (2007) Cell culture process development: advances in process engineering. Biotechnol Prog 23:46–51CrossRefGoogle Scholar
  12. 12.
    Su WW (2003) Bioreactors, perfusion. Encyclopedia of cell technology. Wiley, New York, pp 978–993Google Scholar
  13. 13.
    Shukla A, Thömmes J (2010) Recent advances in large-scale production of monoclonal antibodies and related proteins. Trends Biotechnol 28:253–261CrossRefGoogle Scholar
  14. 14.
    Kompala D, Ozturk S (2006) Optimization of high density perfusion bioreactors. In: Oztuk S, Hu W-S (eds) Cell culture technology for pharmaceutical and cellular therapies. Taylor and Francis, New York, pp 349–416Google Scholar
  15. 15.
    Voisard D, Meuwly F, Ruffieux PA, Baer G, Kadouri A (2003) Potential of cell retention techniques for large-scale high-density perfusion culture of suspended mammalian cells. Biotechnol Bioeng 82(7):751–765CrossRefGoogle Scholar
  16. 16.
    Ryll T, Dutina G, Reyes A, Gunson J, Krummen L, Etcheverry T (2000) Performance of small scale CHO perfusion cultures using an acoustic cell filtration device for cell retention: characterization of separation efficiency and impact of perfusion on product quality. Biotechnol Bioeng 69(4):440–449CrossRefGoogle Scholar
  17. 17.
    Woodside SM, Boweb BD, Piret JM (1998) Mammalian cell retention devices for stirred perfusion bioreactors. Cytotechnology 28:163–175CrossRefGoogle Scholar
  18. 18.
    Castillo RC, Medrohno RA (2004) Cell retention devices for suspended-cell perfusion cultures. In: Scheper T (ed) Adv Biochem Eng Biotechnol 74:129–169Google Scholar
  19. 19.
    Griffiths JB (1992) Animal cell culture processes—batch or continuous? J Biotechnol 22:21–30CrossRefGoogle Scholar
  20. 20.
    Wang Z, Tan W, Poptic EJ, Belovich J. Feasibility of using a small-scale perfusion bioreactor with a novel cell retention device to inoculate a large-scale bioreactor. In: Conference presentation at the American Chemical Society national meeting, San Francisco, CAGoogle Scholar
  21. 21.
    Chu L, Robinson DK (2001) Industrial choices for protein production by large-scale cell culture. Curr Opin Biotechnol 12(2):180–187CrossRefGoogle Scholar
  22. 22.
    Gagnon P (2012) Technology trends in antibody purification. J Chromatogr A 1221:57–70CrossRefGoogle Scholar
  23. 23.
    Jungbauer A (2013) Continuous downstream processing of biopharmaceuticals. Trends Biotechnol 31:479–492CrossRefGoogle Scholar
  24. 24.
    Beck A, Wurch T, Bailly C, Corvaia N (2010) Strategies and challenges for the next generation of therapeutic antibodies. Nat Rev Immunol 10(5):345–352CrossRefGoogle Scholar
  25. 25.
    Lonberg N, Huszar D (1995) Human antibodies from transgenic mice. Int Rev Immunol 13(1):65–93CrossRefGoogle Scholar
  26. 26.
    Lalonde ME, Durocher Y (2017) Therapeutic glycoprotein production in mammalian cells. J Biotechnol 251:128–140CrossRefGoogle Scholar
  27. 27.
    Gebauer M, Skerra A (2009) Engineered protein scaffolds as next-generation antibody therapeutics. Curr Opin Chem Biol 13(3):245–255CrossRefGoogle Scholar
  28. 28.
    Mullard A (2013) Maturing antibody–drug conjugate pipeline hits 30. Nat Rev Drug Discov 12(5):329–332CrossRefGoogle Scholar
  29. 29.
    Allahyari H, Heidari S, Ghamgosha M, Saffarian P, Amani J (2017) Immunotoxin: a new tool for cancer therapy. Tumour Biol 39(2):1–11, 1010428317692226CrossRefGoogle Scholar
  30. 30.
    Allied Market Research (2014) World biosimilars/follow-on-biologics market—opportunities and forecasts, 2013–2020. Allied Market Research, PortlandGoogle Scholar
  31. 31.
    Gottschalk U, Brorson K, Shukla AA (2012) The need for innovation in biomanufacturing. Nat Biotechnol 30(6):489–492CrossRefGoogle Scholar
  32. 32.
    Gutierrez JM, Lewis NE (2015) Optimizing eukaryotic cell hosts for protein production through systems biotechnology and genome-scale modeling. Biotechnol J 10(7):939–949CrossRefGoogle Scholar
  33. 33.
    Shukla AA, Gottschalk U (2013) Single-use disposable technologies for biopharmaceutical manufacturing. Trends Biotechnol 31(3):147–154CrossRefGoogle Scholar
  34. 34.
    Hollak CE, vom Dahl S, Aerts JM, Belmatoug N, Bembi B, Cohen Y, Collin-Histed T, Deegan P, van Dussen L, Giraldo P, Mengel E, Michelakakis H, Manuel J, Hrebicek M, Parini R, Reinke J, di Rocco M, Pocovi M, Sa Miranda MC, Tylki-Szymanska A, Zimran A, Cox TM (2010) Force majeure: therapeutic measures in response to restricted supply of imiglucerase (Cerezyme) for patients with Gaucher disease. Blood Cells Mol Dis 44(1):41–47CrossRefGoogle Scholar
  35. 35.
    Buyel JF, Twyman RM, Fischer R (2017) Very-large-scale production of antibodies in plants: the biologization of manufacturing. Biotechnol Adv 35:458–665CrossRefGoogle Scholar
  36. 36.
    Rathore AS (2016) Quality by design (QbD)-based process development for purification of a biotherapeutic. Trends Biotechnol 34(5):358–370CrossRefGoogle Scholar
  37. 37.
    Pohlscheidt M, Jacobs M, Wolf S, Thiele J, Jockwer A, Gabelsberger J, Jenzsch M, Tebbe H, Burg J (2013) Optimizing capacity utilization by large scale 3000 L perfusion in seed train bioreactors. Biotechnol Prog 29(1):222–229CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Michael Pohlscheidt
    • 1
  • Robert Kiss
    • 1
  • Uwe Gottschalk
    • 1
  1. 1.Biogen International GmbH, International ManufacturingZugSwitzerland

Personalised recommendations