Principles of Process Research and Chemical Development in the Pharmaceutical Industry

American Journal of Pharmaceutical Education, Fall 1998 by Sindelar, Robert D

OLJAN REPIC. Principles of Process Research and Chemical Development in the Pharmaceutical Industry. East Hanover, NJ: Wiley-Interscience 1998. xvi 213pp., 186figs., 39 tbls., $74.95.

Dr. Repic's book illustrates vividly the art, creativity and science displayed in chemical development and process research in the pharmaceutical industry. As stated nicely by Dr. Thomas Blacklock in the Foreword to the book, "After all, the process to put a new drug on the market only begins with discovery. We have to put the genie in the bottle. For those of you who wish to understand how this can be done, this book is for you."

This reasonably well-written book provides the reader several examples of challenging, complex and varied problems faced in chemical development in nine chapters with such intriguing titles as "The Ideal," "Impure Thoughts," "Going All the Way," "Mirrors," "Au Naturel," and "Radiant." The topics selected reflect the strong synthetic organic and analytical chemistry knowledge-base required by the process chemist, yet provided in a fairly readable fashion that may furnish insight to and be enjoyed by a broader chemical/pharmaceutical audience.

The initial chapter utilizes two practical examples to help illustrate the author's view of "The Ideal," the basic principles of process chemistry and chemical development. "Impure Thoughts," Chapter 2, provides 20 referenced examples with necessary simplified reaction schemes that introduce the challenging task of troubleshooting impurities generated in a reaction. Chapters 3, 4 and 5 deal with stereochemical issues in one way or another. These range from the 10 year study ("Going All the Way") of a racemic HMGCoA reductase inhibitor with diastereomeric ratio concerns that made it onto the market to various methods for resolution of enantiomers ("Resolutions") and asymmetric synthesis of pure enantiomers ("Au Naturel"). Chapter 7, "Radiant," is a brief overview to the strategy of introducing isotopic labeling into drugs to study their metabolic fate and distribution in the body.

The final two chapters differ in their focus from Chapters 1-7. Chapter 8, "License", provides a brief overview of the government regulatory process. Good manufacturing practices and validation are discussed in detail. "The Future," Chapter 9, tackles the always difficult task of speculating about the future; the future of chemical development. This very short chapter stresses the promise of monoclonal antibody technology as custom-designed catalysts for bulk chemical processes.

A strength of this moderately priced volume is that it impresses upon the reader what must be some of the pride and enjoyment experienced by working process development chemists. This is an area of the pharmaceutical industry that is little discussed in undergraduate and graduate courses. While targeted to chemists, chapter topics generally give the average reader new to chemical development a good glimpse at the most challenging problems faced in this area.

Robert D. Sindelar

University of Mississippi