Fall 2024 ChBE Seminar: McMullen & Wyvratt

This seminar provides an in-depth exploration of the critical role that chemical engineers play in drug substance process development, scale-up, and manufacturing of active pharmaceutical ingredient (API). By applying fundamentals to solve complex problems and establishing new, innovative methodologies and technologies, chemical engineers are altering the industry’s approach towards building these life-saving therapies. Several case studies from Merck’s Small Molecule Process Research & Development will be presented to highlight the range of challenges commonly encountered by chemists and engineers in the pharmaceutical industry and the approaches used to solve them. 

 

A comprehensive overview of how chemical engineers actively shape pharmaceutical process development at Merck will be provided, using the development of a commercial product to exemplify the pivotal role in chemical engineering to create robust and sustainable manufacturing routes. As will be reviewed, achieving aspirational drug substance processes requires core reaction engineering to commercialize nascent technologies, such as photochemistry and biocatalysis, and a systems engineering approach to establish a successful control strategy for multi-step syntheses. The discussion will then focus on the development and application of innovation and transformative methodologies to enhance process development and our approach to chemical process research.  Discussions around the impact of data-rich experimentation, process modelling, machine-assisted process development, and dynamic flow reaction operations will highlight the resource-sparing knowledge gains through innovation. We will conclude with a outlook on the direction of drug substance process development in the industry, delving into the pressing challenges where chemical engineers are well-poised to offer greater impact.

Jonathan McMullen graduated from Lehigh University in 2005 with dual Bachelor of Science degrees in Chemical Engineering and Integrated Business and Engineering.  He pursued his graduate studies at MIT under the guidance of Professor Klavs Jensen.  His PhD thesis research focused on the design and development of integrated microreactor systems for automated reaction development using direct search and model-based optimization algorithms.  In 2010, he joined the Chemical Engineering Research and Development Department of Merck & Co., Inc. and has had roles of increasing responsibility in process development, operations and manufacturing, and technology development within Small Molecule Process Research & Development. Notably, he served as technical lead for developing and commercializing drug substance processes that leverage unique, enabling technologies, such as flow chemistry, immobilized biocatalysis, and photochemistry.  He is recognized throughout the pharmaceutical industry for subject matter expertise in reaction engineering, kinetic modeling, and scale-up as exemplified in his 30 publications.  He is the recipient of the inaugural AIChE Pharmaceutical Discovery Development and Manufacturing Excellence Award in Technical Innovation and the ACS Green Chemistry Institute Pharmaceutical Roundtable Peter J Dunn Award for Green Chemistry and Engineering Impact in the Pharmaceutical Industry (2021) He is currently a Senior Principal Scientist, where he is responsible for leading engineering process development on clinical assets and the department’s scientific excellence.  

 

Brian Wyvratt graduated from Lehigh University in 2011 with a Bachelor of Science degree in Chemical Engineering. He went on to continue his graduate studies at the University of Michigan advised by Professor Levi Thompson. His PhD research explored structure-function relationships of early-transition metal carbides and nitrides as heterogeneous catalysts and catalytic supports, leveraging model reactions aligned with renewable energy applications. He joined the Chemical Engineering Research and Development department at Merck & Co., Inc. in Rahway, NJ in late 2016. His experiences have spanned across individual contributor lab engineer, pilot plant facility lead, and engineering program/project lead. He has a passion for integrating novel technologies into drug substance process development for efficiency and knowledge-capture bonuses. He is currently a Principal Scientist, where he is responsible for leading the drug substance development on a current clinical asset.