Enantiopure drugs, manufacture

Pharmaceutical manufacturers began to develop technologies either to resolve or selectively synthesize enantiopure drugs. The justification was that the active enantiopure drug would prove to be more efficacious, and this would allow drug companies to extend expiring originator patents. 

In order to illustrate an example of process design for the manufacture of enantiopure drug substances on an industrial SMB system, consider manufacturing 10 ton/ year of an enantiopure drug. The racemic drug by definition is a 50 50 mixture of each enantiomer (products A and B). The goal is to process enantiopure drug substances in order to obtain 99 % purity for both the extract and the raffinate. 

Preparative chromatography has been used for chiral separations for years, but examples of multi-kg separations (and hence larger ones) were rare until recently. The development of SMB techniques (both hardware and simulation software) has made major breakthroughs in this field. The ability of SMB as a development tool has allowed the pharmaceutical manufacturer to obtain kilo grams quantities of enantiopure drug substances as well benefit from the economics of large-scale production. 

From the position of the FDA, acceptance of SMB as a viable tool for cGMP manufacturing of enantiopure drug substances, there shall be no compromise, it must be properly engineered, and follow established guidelines. 

---