Dr. Jamie McCabe Dunn

Dr. Jamie McCabe Dunn
Director of Process Chemistry
Merck
Abstract

Manipulating Macrocycles: The Development Synthesis of Sugammadex (Bridion ®)

Upon the approval of Bridion® by the US FDA in 2015, there was a rapid surge in patient demand, which the original commercial synthetic route (GEN1) struggled to consistently meet. The GEN1 chemistry route encountered a 40% rate of batch failures due to the emergence of an unqualified impurity and an API crystallization process dependent on kinetic nucleation, leading to an inability to achieve the desired residual solvent specification. Beyond these challenges, the process did not align with Merck’s commitment to green and sustainable commercial processes, exhibiting inefficiency, high Product to Mass Intensity (PMI), and generating unnecessary waste through discards or reprocessing of failed batches. This prompted the initiation of a second generation (GEN2) commercial process definition team, charged with creating a robust and sustainable process to stabilize the supply chain and progress towards Merck’s environmental sustainability objectives. The GEN2 synthesis developed at Merck significantly enhanced process efficiency by increasing the overall yield by 31% and reducing the PMI of the entire process by 37%. Furthermore, the improved process and control strategy prevented the formation of the unidentified impurities and enhanced the overall purity. The implementation of the GEN2 process has achieved a 100% success rate on both development and commercial scales, receiving approval in the EU in 2021, the US in 2022, and in seven other countries to date.

Jamie McCabe Dunn

Jamie McCabe Dunn earned her PhD from the University of Pittsburgh under the guidance of Professor Kay Brummond, and subsequently held a postdoctoral position at the University of Colorado in the group of Professor Andrew Phillips. In 2009, Jamie commenced her career at Merck in Process Chemistry, and in 2017, she took on the role of Scientific Lead for Bridion®. Her work was distinguished with the prestigious Heroes of Chemistry Award for 2023 by the American Chemical Society. Currently, Jamie serves as the Director of Process Chemistry in Rahway, NJ, where she leads a dedicated team of process chemists focused on the commercial route definition for two oncology therapeutics. In addition to her significant scientific and pipeline achievements, Jamie has earned three individual ACS awards: the 2022 Rising Star Award, the 2019 Rising Star of Medicinal Chemistry, and the 2018 ACS Young Investigator Award. She also holds a position on the editorial advisory board of the journal Organic Process Research and Development and serves as a co-editor in the special issue ‘Celebrating Women in Process Chemistry.’

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