Chapter 13 : Manufacture of Mammalian Cell Biopharmaceuticals

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This chapter presents a review on important aspects of the manufacturing of biopharmaceuticals in mammalian systems. These include recovery, purification, formulation, fill and finish, bioanalytics, and current Good Manufacturing Practices (cGMP). Purification process optimization must examine the operation of units in concert with one another, and the ultimate goal is to make as much purified product as possible by the cheapest, quickest, most reproducible, and most robust and efficient route. Viral contamination is a risk to all biopharmaceutical products (including MAbs) derived from cell lines of human or animal origin. The goals of cGMP can be summarized as: protect the product from contamination; prevent mix-ups; know what you are to do before you do it; document what really happens; strive for consistency and control; have an independent group make the final decisions; and solve problems, learn from mistakes, monitor, and continuously improve. MAb manufacturers prepare written validation plans or protocols that specify procedures, tests, and necessary data and analyses. In the manufacture under cGMP guidelines, raw materials (RMs) need to be characterized and released to ensure that they meet predefined specifications on their quality. Manufacture of biopharmaceutical is governed by various cGMP regulations, requiring validation of process, qualification/release of all raw materials (RMs), and thorough testing/release of cell banks and products to ensure safety and potency. Costs are high for production using mammalian cell systems due to expensive facilities, equipment, RMs, testing, validation, etc. Alternative operation approaches are emerging, including incorporation of more single-use devices and outsourcing.

Citation: Zhang J. 2010. Manufacture of Mammalian Cell Biopharmaceuticals, p 179-195. In Baltz R, Demain A, Davies J, Bull A, Junker B, Katz L, Lynd L, Masurekar P, Reeves C, Zhao H (ed), Manual of Industrial Microbiology and Biotechnology, Third Edition. ASM Press, Washington, DC. doi: 10.1128/9781555816827.ch13

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High-Performance Liquid Chromatography
Murine leukemia virus
Enzyme-Linked Immunosorbent Assay
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