Pharmaceuticals recombinant

M. Mumenthaler, C. C. Hsu, and R. Pearlman, Feasibility study on spray-drying protein pharmaceuticals recombinant human growth hormone and tissue-type plasminogen activator, Pharm. Res, 11(1), 12 (1994). 

Mumenthaler M, Hsu CC, and Pearlman R. Feasibility study on Spray-drying Protein Pharmaceuticals Recombinant Human Growth Hormone and Tissue-type Plasminogen Activator. Pharm Res 1994 11(1) 12—20. 

Bacterial pharmaceutical products include antibiotics, antitumor agents, immunomodulators, and enzyme inhibitors. Other bioactive products of bacterial origin are coccidiostatic agents, nematicides, and insecticides. In addition, Escherichia coli, the prototype of molecular biology, is one of the most important hosts for the production of pharmaceutical recombinant proteins. 

Farm animals produce recombinant proteins less expensively than bacteria or cells in culture because the farm animals produce large volumes of milk containing up to 5 g/L of recombinant protein. In addition, modifications to the proteins that can be performed only by mammalian cells are made by the cells of the mammary gland. Therefore, numerous pharmaceuticals that previously could only be made by cells in culture or extracted from human tissue or blood are being produced by lactating farm animals. 

U.S.A., in lactating dairy cattie to increase milk production. EH Lilly and Company, The Upjohn Company, and American Cyanamid Company also have interests in the commercial appHcation of recombinant bovine GH. Recombinant porcine GH [9061-23-8] preparations from several companies, eg. The Upjohn Company, Smith Kline Beecham Animal Health, Pitman-Moore, Inc., Monsanto Company, and American Cyanamid Company, are being evaluated for commercial use. Recombinant human GH for clinical use is marketed under such names as Protropin (Genentech), Umatrope (EH Lilly), Genotropin (Sumitomo), and Somatonorm (Kabi-Vitmm) by a variety of pharmaceutical companies. A listing of additional suppHers is available (2). 

H. Y. Aboul-Enein, in S. Ahuja, ed.. Chromatography of Pharmaceuticals Natural, Synthetic, and Recombinant Products, American Chemical Society, Washington, D.C., 1992, pp. 111-120. 

It is often important to control the CSD of pharmaceutical compounds, eg, in the synthesis of human insulin, which is made by recombinant DNA techniques (1). The most favored size distribution is one that is monodisperse, ie, all crystals are of the same size, so that the rate at which the crystals dissolve and are taken up by the body is known and reproducible. Such uniformity can be achieved by screening or otherwise separating the desired size from a broader distribution or by devising a crystallization process that will produce insulin in the desired form. The latter of these options is preferable, and considerable effort has been expended in that regard. 

Regulatory agencies currently set stringent standards on the quantities of nucleic acids allowed in recombinant biological products. In the pharmaceutical industry these requirements necessitate the quantification of trace amounts of nucleic acids in the presence of large quantities of protein and other excipients. Flourescence methods offer advantages for such analyses, but also have limitations. The use of a variety of fluorescent dyes and techniques is described here, and practical examples of such use are presented. 

Stirred tank models have been widely used in pharmaceutical research. They form the basis of the compartmental models of traditional and physiological pharmacokinetics and have also been used to describe drug bioconversion in the liver [1,2], drug absorption from the gastrointestinal tract [3], and the production of recombinant proteins in continuous flow fermenters [4], In this book, a more detailed development of stirred tank models can be found in Chapter 3, in which pharmacokinetic models are discussed by Dr. James Gallo. The conceptual and mathematical simplicity of stirred tank models ensures their continued use in pharmacokinetics and in other systems of pharmaceutical interest in which spatially uniform concentrations exist or can be assumed. 

The significance of protein oxidation became paramount with the advent of recombinant protein biologies used as human therapeutics. Careful characterization of protein stability is essential to maintaining the efficacy of protein pharmaceuticals. If even a single side chain amino acid residue becomes oxidized, then a protein therapeutic may not have the same activity in vivo as the unmodified protein. 

This chapter provides an overview of the tools that have been developed and optimized specifically for the production of pharmaceuticals in alfalfa, with the emphasis on recent technological breakthroughs. The ability of alfalfa leaves to produce complex recombinant proteins of pharmaceutical interest is discussed and illustrated with recent data obtained in our laboratories. Data are presented concerning the production and characterization of alfalfa-derived C5-1, a diagnostic anti-human... 

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