Large-scale synthesis of peptides

Recent advances in the areas of formulation and delivery have rekindled the interest of the pharmaceutical community in peptides as drug candidates, w hich, in turn, had provided a challenge on the peptide industry to develop efficient methods for the manufacture of relatively complex peptides on sca les of up to metric tons per year. This article focuses on chemical synthes is approaches for peptides, and presents an overview of the methods availab le and in use currently, together with a discussion of scale-up strategies. Examples of the different methods are discussed, together with solutions t o some specific problems encountered during scale-up development. Finally, an overview is presented of issues common to all manufacturing methods, i.e ., methods used for the large-scale purification and isolation of final bul k products and regulatory considerations to be addressed during scale-up of processes to commercial levels. (C) 2000 John Wiley & Sons, Inc.