Manufacturing Recombinant Protein Biopharmaceuticals

In contrast to the biopharmaceuticals discussed thus far (recombinant proteins and gene therapy products), antisense oligonucleotides are manufactured by direct chemical synthesis. Organic synthetic pathways have been developed, optimized and commercialized for some time, as oligonucleotides are widely used reagents in molecular biology. They are required as primers, probes and for the purposes of site-directed mutagenesis. 

Any mammahan ceU line has the basic machinery to express and secrete recombinant protein, and huge numbers of ceU fines with suitable growth properties are available from various tissues and species. The smaU number of cell fines industrially used for manufacturing is, therefore, surprising. Two hamster cell fines, the Chinese hamster ovary cell fine (CHO) and the baby hamster kidney cell fine (BHK), and two geneticaUy related mouse cell fines, the myeloma NSO derived from BALB/c mice, and the hybridoma SP2-0, a fusion of the myeloma with B cells from the same mouse strain, supply most of the mammalian ceU-based biopharmaceuticals, whether marketed or still under development Once commonly accepted as producers, a large body of information about... 

The main focus on modem biopharmaceuticals should be directed towards novel products which will be either monoclonal antibodies, recombinant proteins, cell and gene therapeutics, or viral products. Apart from product classes, new approaches to manufacture are also advancing, with transgenic animals and plants complementing existing cell culture-based expression (see Part IV, Chapters 5-11). (For a recent review, see Ref [8].)... 

Plants are a potentially cheap source of biopharmaceuticals. It has been estimated that the manufacturing costs for recombinant proteins in plants could be 10- to 50-fold lower than the same product obtained by fermentation with E. coll and subsequent recovery. 

Zhang J, Reddy J, Salmon P, et al. (1998). Process characterization studies to facilitate validation of a recombinant protein fermentation. In B D Kelley, R A Ramelmeier (eds.), Validation of Biopharmaceutical Manufacturing Processes. ACS Symposium Series. 698 12-27. 

This section briefly overviews how biopharmaceutical substances are produced in a biopharmaceutical/biotech manufacturing facility. As the vast bulk of biopharmaceuticals are proteins synthesized in recombinant prokaryotic (e.g. E. coli) or eukaryotic (e.g. mammalian cells) production systems, attention will focus specifically upon these. 

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