Challenges in the development of an efficient enzymatic process in the pharmaceutical industry

3.9 Scale-Up and Development of Enzyme-Based Processes for Large-Scale Synthesis Applications

“…Frequently, this is a step that is overlooked until late in process development, and only limited scientific studies have been reported (see, for example, ref [59] ). The extent of purification will be dependent upon the market and final application of the product, but the preceding steps of concentration and isolation require attention and are heavily influenced by the biocatalytic reaction step.…”

Homogeneous, Enzyme, and Polymerization Catalysis

“…Resource limitations currently impede application of biocatalytic processes in industry. That is, product quality control, enzyme lifetime, and downstream product separation, which require complex reactors and separation schemes, depend on highly complex variables that are difficult to design for and control (Schoemaker et al, 2003;Yazbeck et al, 2004). Second, the scope of available enzyme reactions and substrates is limited, even with the discovery of many new enzymes and the development of non-aqueous processes; this is especially a problem for reactions involving the formation of carbon-carbon bonds (Schoemaker et al, 2003).…”

“…While improvements in enzyme engineering, biocatalyst immobilization techniques, and enzyme chemistry are on the increase, improvements in reactor and separation technologies for biocatalytic applications have lagged (Yazbeck et al, 2004). While improvements in enzyme engineering, biocatalyst immobilization techniques, and enzyme chemistry are on the increase, improvements in reactor and separation technologies for biocatalytic applications have lagged (Yazbeck et al, 2004).…”

“…The use of directed enzyme evolution should prove to be the best method to develop the next generation of biocatalysts (Zhao et al, 2002;Kirk et al, 2002;Cherry and Fidantsef, 2003;Schoemaker et al, 2003), although rational protein engineering should continue to be important. Examples are the application of enzymes in organic solvents and membrane systems to processes in which traditional separation techniques are ineffective and where the unique selectivity of enzymes is required, such as low-cost separations of organic acids and alcohols (Rethwisch and Dordick, 1991;van Beilen and Li (2002);Yazbeck et al, 2004). The high cost and difficulty of regenerating coenzymes and cofactors has impeded the commercial application of enzyme catalysts.…”

Choice of biocatalyst form for scalable processes

“…Currently, approx. 150 processes are operating industrially with a mix of whole-cell and isolated enzyme catalysts [4][5][6]. The focus now has shifted to discovery of new enzymes and their implementation in chemical syntheses in industry.…”