New frontiers in cell line development: Challenges for biosimilars

Hou, Jeff Jia Cheng, Codamo, Joe, Pilbrough, Warren, Hughes, Benjamin, Gray, Peter P. and Munro, Trent P. (2011) New frontiers in cell line development: Challenges for biosimilars. Journal of Chemical Technology and Biotechnology, 86 7: 895-904. doi:10.1002/jctb.2574

Author Hou, Jeff Jia Cheng
Codamo, Joe
Pilbrough, Warren
Hughes, Benjamin
Gray, Peter P.
Munro, Trent P.
Title New frontiers in cell line development: Challenges for biosimilars
Journal name Journal of Chemical Technology and Biotechnology   Check publisher's open access policy
ISSN 0268-2575
Publication date 2011-07-01
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1002/jctb.2574
Volume 86
Issue 7
Start page 895
End page 904
Total pages 10
Place of publication West Sussex, United Kingdom
Publisher John Wiley & Sons
Language eng
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.
Keyword Biosimilars
Cell line engineering
Monoclonal antibody
Single-use bioreactors
Transient gene expression
Q-Index Code CX
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Non HERDC
ERA White List Items
Australian Institute for Bioengineering and Nanotechnology Publications
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Citation counts: TR Web of Science Citation Count  Cited 15 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 19 times in Scopus Article | Citations
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Created: Sat, 01 Oct 2011, 01:07:57 EST by Mr Benjamin Hughes on behalf of Aust Institute for Bioengineering & Nanotechnology