Introduction to Process Chemistry: Summary and Further Reading
Comparison between medicinal and process chemistry highlights some of the key differences between small scale research and scaling up – moving towards commercial production. Upon scaling up from laboratory research to larger scale production, there are a number of factors that need to be taken into consideration. Table 1 summarizes the SELECT criteria along with the associated considerations and potential issues.
| Criteria | Sub-criteria | Examples of Potential Issues |
|---|---|---|
| Safety | Process safety | Explosions |
| Exposure to harmful substances | Carcinogens, sensitisers | |
| Environmental | Wasted resources | Quantity & variety of solvents |
| Substances harmful to the environment | Aquatic toxins, ozone depleters | |
| Legal | Infringement of Intellectual Property | Competitor patenting key intermediate |
| Regulation of reagents and intermediates | ||
| Economic | Meeting Cost of Good (profit margin) | Long synthesis or expensive starting materials |
| Investment costs (equipment) | ||
| Control | Control of quality | Meeting specifications/ GMP |
| Control of physical/chemical parameters | ||
| Throughput | Time scale of manufacture | Long synthetic route |
| Availability of starting materials | Rare natural products |
Table 1: The SELECT criteria with associated potential issues.
Recommended reading:
- M. Butters, D. Catterick, A. Craig, A. Curzons, D. Dale, A. Gillmore, S. P. Green, I. Marziano, J. – P. Sherlock and W. White, Critical Assessment of Pharmaceutical Processes – A Rationale for Changing the Synthetic Route, Chem. Rev., 2006, 106, 3002-3027.
- J. Blacker and M. T. Williams, Pharmaceutical Process Development : Current Chemical and Engineering Challenges, Royal Society of Chemistry, Cambridge, 2011.
- T. Y. Zhang, Process Chemistry: The Science, Business, Logic, and Logistics, Chem. Rev., 2006, 106, 2583-2595.
- P. J. Dunn, The importance of Green Chemistry in Process Research and Development, Chem. Soc. Rev., 2012, 41, 1452-1461.
- H. – J. Federsel, Chemical Process Research and Development in the 21st Century: Challenges, Strategies, and Solutions from a Pharmaceutical Industry Perspective, Acc. Chem. Res., 2009, 42, 671-680.
- MedChem Tips and Tricks – a general guide, developed by the ACS GCI PR, to making all parts of pharmaceutical development more sustainable.