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Keywords:

  • biosimilars;
  • cell line engineering;
  • CHO;
  • monoclonal antibody;
  • biopharmaceutical;
  • biologic;
  • single-use bioreactors;
  • transient gene expression

Abstract

Worldwide sales of biologic drugs exceeded US$ 92 billion in 2009. With many biopharmaceutical patents expiring over the next decade, a wave of second-generation or ‘follow-on’ biologics will be vying for market share and regulatory approval. Patents cover not only the drugs, but also the molecular modalities that facilitate their high-level expression. Companies have historically relied on gene amplification to create productive cell lines, yet this lengthy and imprecise process usually leads to extensive variation and unpredictable stability of expression. Biosimilar manufacturers must therefore decide whether traditional methods of cell line development will suffice or if emerging technologies can provide greater reproducibility and speed. Volumetric yields of 1–2 g L−1 are adequate for most production processes and the focus has shifted towards reliable and predicable product quality attributes over maximum possible titres. Recent advances in this area include cell lines with targeted genetic modifications, alternative production hosts such as PER.C6® or yeast, and engineered expression vectors, including the UCOE and Selexis platforms. Host cell engineering, single-use technologies, and rapid transient gene expression are also likely to be enablers of biosimilars. Given the well-known biologics industry mantra ‘the process defines the product’, it remains to be seen how novel cell line development strategies will affect product equivalence and regulatory approval in a biosimilars context. Some recent advances in the field and how they relate to biosimilars are explored. Copyright © 2011 Society of Chemical Industry