Bioseparations

Manufacturing approaches for selected bioproducts of the new biotechnology impact product recovery and purification. The most prevalent bioseparations method is chromatography (qv). Thus the practical tools used to initiate scaleup of process Hquid chromatographic separations starting from a minimum amount of laboratory data are given. 

The three main sources of competitive advantage in the manufacture of high value protein products are first to market, high product quaUty, and low cost (3). The first company to market a new protein biopharmaceutical, and the first to gain patent protection, enjoys a substantial advantage. The second company to enter the market may find itself enjoying only one-tenth of the sales. In the absence of patent protection, product differentiation becomes very important. Differentiation reflects a product that is purer, more active, or has a greater lot-to-lot consistency. 

Product Year approved Selling price, /g Quantity for 200 X 10 in sales, kg 

Adapted from Ref. 2 with additional data from Ref. 4. 

Biosynthetic Human Insulin from E. coli. Insulin [9004-10-8] a polypeptide hormone, stimulates anaboHc reactions for carbohydrates, proteins, and fats thereby producing a lowered blood glucose level. Porcine insulin [12584-58-6] and bovine insulin [11070-73-8] were used to treat diabetes prior to the availabiHty of human insulin [11061 -68-0]. AH three insulins are similar in amino acid sequence. EH LiHy s human insulin was approved for testing in humans in 1980 by the U.S. EDA and was placed on the market by 1982 (11,12). 

Human insulin was the first animal protein to be made in bacteria in a sequence identical to the human pancreatic peptide. Expression of separate insulin A and B chains were achieved in Escherichia co/i K-12 using genes for the insulin A and B chains synthesized and cloned in frame with the 

We have studied a variety of separation processes and techniques. Our focus was on developing an elementary understanding of an individual separation process/tech-nique. In practice, more often than not, a combination of more than one separation process is employed, regardless of the scale of operation involved. Here we introduce very briefly the separation sequences employed in a few specific industries. The separation sequences of interest are considered under the following headings bioseparations (Section 11.1) water treatment (Section 11.2) chemical and petrochemical industries (Section 11.3) hydrometal-lurgical processes (Section 11.4). It is to be noted here that often the separation sequences are reinforced by chemical reactions within such a sequence or before/after the separation steps. The intent here is to provide an elementary view of the complexity and demands of practical systems where certain types of separation sequences are crucial/ primary/dominant components. 

Category Bioproduct example Molecular weight Physical dimension 

Smaller molecules Ethanol, acetone, n-butanol, acetic acid, citric acid, lactic acid, butanediol, amino acids, glucose, fructose Generally less than 200  

Somewhat larger molecules Antibiotics, steroids, disaccharides, larger fatty acids Generally less than 600-700 but greater than 200  

Macromolecules Proteins (enzymes), polysaccharides, nucleic acids 10 to 10  

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The design of bioseparation unit operations is influenced by these governmental regulations. The constraints on process development grow as a recovery and purification scheme undergo licensing for commercial manufacture. 

P. R. Foster, in L. R. Weathedey, ed.. Engineering Processes For Bioseparations, Butterworth-Heineman, Oxford, in press. 

Techniques used in bioseparations depend on the nature of the product (i.e., the unique properties and characteristics which provide a handle for the separation), and on its state (i.e., whether soluble or insoluble, intra- or extracellular, etc.). All early isolation and recovery steps remove whole cells, cellular debris, suspended solids, and colloidal particles, concentrate the product, and, in many cases, achieve some degree of purification, all the while maintaining high yield. For intracellular compounds, the initial harvesting of the cells is important... 

TosoHaas The Bioseparation Specialist—TSK-Gel, Toyo Pearl, Amberchrom. 

We believe that better understanding of the behavior of macromolecules at the solid surfaces will facilitate further progress in chemical design of the composite sorbents as well as other bioseparation media such as membranes, fibers etc. and their application in various fields. 

The equilibrium constant is defined by K, K = y/x, and the portion coefficient is also defined by K as a ratio of CAu/CA1 which is constant. Based on the value of K, single or multi-stage extractions are performed to do a perfect job in bioseparation. 

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