Scott Quirie is an associate scientist in the Chemical Engineering R&D department at Merck in Rahway, NJ. He is currently part of the Small Scale Organics Pilot Plant, focusing on batch planning and execution to advance the scale-up of small molecule pipeline candidates. Prior to this, Scott was a member of the Crystallization Lab, where he leveraged PAT to develop isolation processes for a number of Merck’s late-stage drugs. He obtained his bachelor’s degree in Chemical Engineering from the New Jersey Institute of Technology in 2018.
Two Approaches to Effective Particle Size and Impurity Control
Crystal Engineering Islatravir
Islatravir (MK-8591), a highly potent nucleoside reverse transcriptase translocation inhibitor, is being developed by Merck to stem the spread of global HIV infections. Following a nine-enzyme in-vitro synthesis from 2-ethynylglycerol without intermediate isolation, a crude active pharmaceutical ingredient with high levels of biological and chemical impurities must be purified through recrystallization. As a potent compound with efficacy at sub-milligram doses, islatravir requires a robust crystallization process for consistent particle size to meet content uniformity requirements in a tablet.
Two robust crystallization methods were developed and scaled-up that both delivered a controlled particle size distribution (PSD) and improved impurity profile. The first process implements jet-milled seed to control PSD, an effective yet costly approach that also posed industrial hygiene concerns. Due to elucidating the crystallization mechanism, dry milling was able to be avoided in the second process with a novel shear-induced nucleation and thermal annealing crystallization (SINTAX). The SINTAX process promotes secondary nucleation via wet milling and simultaneous antisolvent charge, followed by a thermal annealing phase to dissolve fines and improve purity. In this presentation, we compare the impacts of the two crystallization processes on impurity rejection, PSD, and processability.
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Scott Quirie - Merck & Co, Inc.
