From 2006 to 2011, an average of 15 novel recombinant protein therapeutics\r\nhave been approved by US Food and Drug Administration (FDA) annually. In addition, the\r\nexpiration of blockbuster biologics has also spurred the emergence of biosimilars. The\r\nincreasing numbers of innovator biologic products and biosimilars have thus fuelled the\r\ndemand of production cell lines with high productivity. Currently, mammalian cell line\r\ndevelopment technologies used by most biopharmaceutical companies are based on either\r\nthe methotrexate (MTX) amplification technology or the glutamine synthetase (GS)\r\nsystem. With both systems, the cell clones obtained are highly heterogeneous, as a result of\r\nrandom genome integration by the gene of interest and the gene amplification process.\r\nConsequently, large numbers of cell clones have to be screened to identify rare stable high\r\nproducer cell clones. As such, the cell line development process typically requires 6 to 12\r\nmonths and is a time, capital and labour intensive process. This article reviews established\r\nadvances in protein expression and clone screening which are the core technologies in\r\nmammalian cell line development. Advancements in these component technologies are\r\nvital to improve the speed and efficiency of generating robust and highly productive cell\r\nline for large scale production of protein therapeutics.
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