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Pharmaceuticals 2013, 6(5), 579-603; doi:10.3390/ph6050579

Advances in Mammalian Cell Line Development Technologies for Recombinant Protein Production

Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01, Centros, 138668, Singapore
School of Chemical and Biomedical Engineering, Nanyang Technological University, N1.2-B2-33, 62 Nanyang Avenue, 637459, Singapore
Department of Pharmacy, Faculty of Science, National University of Singapore, Singapore
Author to whom correspondence should be addressed.
Received: 1 March 2013 / Revised: 28 March 2013 / Accepted: 10 April 2013 / Published: 26 April 2013
(This article belongs to the Special Issue Biologics)
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From 2006 to 2011, an average of 15 novel recombinant protein therapeutics have been approved by US Food and Drug Administration (FDA) annually. In addition, the expiration of blockbuster biologics has also spurred the emergence of biosimilars. The increasing numbers of innovator biologic products and biosimilars have thus fuelled the demand of production cell lines with high productivity. Currently, mammalian cell line development technologies used by most biopharmaceutical companies are based on either the methotrexate (MTX) amplification technology or the glutamine synthetase (GS) system. With both systems, the cell clones obtained are highly heterogeneous, as a result of random genome integration by the gene of interest and the gene amplification process. Consequently, large numbers of cell clones have to be screened to identify rare stable high producer cell clones. As such, the cell line development process typically requires 6 to 12 months and is a time, capital and labour intensive process. This article reviews established advances in protein expression and clone screening which are the core technologies in mammalian cell line development. Advancements in these component technologies are vital to improve the speed and efficiency of generating robust and highly productive cell line for large scale production of protein therapeutics. View Full-Text
Keywords: cell line development; protein expression; clone screening; biopharmaceutical production cell line development; protein expression; clone screening; biopharmaceutical production

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Lai, T.; Yang, Y.; Ng, S.K. Advances in Mammalian Cell Line Development Technologies for Recombinant Protein Production. Pharmaceuticals 2013, 6, 579-603.

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