Small molecule drug manufacture

Organic Chemistry Synthesis Route The production of the API for small molecule drugs requires ingenious and meticulous development of organic synthesis steps. Some drugs may require more than 50 steps to obtain the intended API. For example, there are more than 100 production steps for the manufacture of Roche s AIDS drug enfuvirtide (Fuzeon), approved by the FDA in March 2003 see Exhibit 10.1. 

The use of Process Analytical Technology (PAT) to fully characterize and control the manufacturing process may enable the biotechnology industry in the not too distant future to produce these complex molecules as cheaply and efficiently as traditional small molecule drugs. 

Although there is much to be optimistic about the future of protein pharmaceuticals, there are still many unique problems with their development, production, and delivery. Among the more obvious problems with protein drugs is the fact that they are much more delicate than small-molecule drugs. Proteins such as hormones, antibodies, and enzymes cannot normally be compounded or pressed into dry pills or emulsified or concentrated into tinctures. This type of conventional pharmaceutical manufacturing and formulation would destroy the activity of most protein pharmaceuticals. Similarly most peptide hormones, antibodies, and enzymes cannot be stored indefinitely at room temperatures in nonsterile containers instead they must be kept in a cool, dark, aqueous, sterile environment for no more than a few weeks. These limitations to protein preparation and formulation have created a significant challenge to pharmaceutical chemists. Potential solutions to these problems are discussed in Chapter 4 of this book. 

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