Cheol K. Chung

Cheol K. Chung
Principal Scientist
Process Research & Development
Merck Research Laboratories
Rahway, NJ
Host: Tao Wang

Abstract

Process R&D for Sustainable Pharmaceutical Manufacturing

In this presentation, a process chemist’s perspective toward the development of sustainable manufacturing processes for pharmaceuticals with the ultimate goal of developing ideal chemical process, will be discussed. Achieving this ambitious goal is enabled by a green-by-design development strategy, to progress from initial route design through to a fully optimized sustainable commercial manufacturing process. The strategy commences with the application of green chemistry principles incorporated into route exploration in order to identify the shortest possible routes with maximized atom economy. This is followed by establishing proof of concept demonstration for the different routes with extensive use of high-throughput experimentation, allowing evaluation of vast reaction landscapes with minimal material and solvents. Next, viable routes are carefully evaluated for efficiency and sustainability potential for final route selection supported by computational and predictive science. Lastly, the selected route is fully optimized, with the goal to develop a sustainable process with minimal environmental footprint.

The strategy described above was successfully applied to a number of recent drug development programs, among which process development stories for Letermovir and Nemtabrutinib will be highlighted. Green chemistry mindset focusing on not just the key bond forming reactions, but also encompassing entire supply chains ensures sustainable long-term pharmaceutical manufacturing. Green chemistry mindset also encourages the discovery of novel chemical transformations that are more sustainable, economical and safer to execute. For instance, in Letermovir program, Merck scientists invented a novel hydrogen-bonding catalyst to circumvent the robustness issues encountered during initial scale-up, greatly improving the sustainability represented by low process mass intensity or PMI. The newly developed process reduced the PMI by 70% and the raw material cost by > 90%. In another example of Nemtabrutinib, a novel 2-step synthesis starting from a renewable raw material was developed for a key intermediate, which successfully replaced the existing 11-step sequence while dramatically reducing the PMI by 94%.

Cheol K. Chung

Cheol received his B.S. and M.S. degrees in chemistry from Seoul National University in Korea. He then moved to the United States and obtained Ph.D. degree in organic chemistry under the supervision of Professor Barry Trost at Stanford University. After completing the postdoctoral training in the laboratories of late Professor Robert Grubbs, Cheol joined Merck Process Research in Rahway in 2008, where he has contributed to a number of drug development programs including Anacetrapib, Odanacatib, Niraparib, Letermovir, and most recently, Nemtabrutinib. His main areas of interest are the application of catalytic reactions in organic synthesis, designing efficient and practical synthesis of complex drug candidates, and development of new reactions using high-throughput experimentation.

Jeannette Brown Lectureship

The Department of Chemistry established the Jeannette Brown Lectureship to honor the career and legacy of one of its outstanding alumna. This lectureship will bring experts in all fields of chemistry from around the world to the University of Minnesota, with emphasis on highlighting the work and careers of Black, Indigenous, and people of color in the chemical sciences. The lectureship reflects and celebrates the pioneering work of Jeannette Brown as a talented chemist in the pharmaceutical industry for 25 years, author, historian, and tireless leader and advocate for the inclusion and advancement of African American women in chemistry-related professional pursuits and careers.

This lectureship is sponsored by Merck & Co., Inc., Kenilworth, NJ, USA, and by donations to the Jeannette Brown Lectureship Fund. Supporters can go to the Department of Chemistry’s giving page to donate.

Alumna Jeannette Brown

Brown is the first African American to receive a degree from the Department of Chemistry's graduate program, earning her master's degree in 1958. She is a former faculty associate in the Department of Pre-College Programs at the New Jersey Institute of Technology. For 25 years, she worked as a research chemist at Merck. She is the author of two books, "African American Women Chemists" and "African American Women Chemists in the Modern Era." She is a Société de Chimie Industrielle (American Section) Fellow of the Chemical Heritage Foundation (2004), and is a member of the first class of American Chemical Society (ACS) Fellows (2009). For her distinguished service to professionalism, she received the Henry Hill Award from the ACS Division of Professional Relations in 2020. For her work as a mentor to minority students and science education advocacy, she was elected to the Hunter College Hall of Fame in 1991; was honored by the University of Minnesota with an Outstanding Achievement Award in 2005; and received the ACS national award for Encouraging Disadvantaged Students into Careers in the Chemical Sciences in 2005.