Kilogram-scale prexasertib monolactate monohydrate synthesis under continuous-flow CGMP conditions
2017; American Association for the Advancement of Science; Volume: 356; Issue: 6343 Linguagem: Inglês
10.1126/science.aan0745
ISSN1095-9203
AutoresKevin P. Cole, Jennifer McClary Groh, Martin D. Johnson, Christopher L. Burcham, Bradley M. Campbell, William D. Diseroad, Michael R. Heller, John R. Howell, Neil J. Kallman, Thomas M. Koenig, Scott A. May, Richard D. Miller, David Mitchell, David P. Myers, Steven S. Myers, Joseph L. Phillips, Christopher S. Polster, Timothy White, Jim Cashman, D. Declan Hurley, Robert Moylan, Paul Sheehan, Richard D. Spencer, Kenneth W. Desmond, P. A. Desmond, Olivia Gowran,
Tópico(s)3D Printing in Biomedical Research
ResumoAdvances in drug potency and tailored therapeutics are promoting pharmaceutical manufacturing to transition from a traditional batch paradigm to more flexible continuous processing. Here we report the development of a multistep continuous-flow CGMP (current good manufacturing practices) process that produced 24 kilograms of prexasertib monolactate monohydrate suitable for use in human clinical trials. Eight continuous unit operations were conducted to produce the target at roughly 3 kilograms per day using small continuous reactors, extractors, evaporators, crystallizers, and filters in laboratory fume hoods. Success was enabled by advances in chemistry, engineering, analytical science, process modeling, and equipment design. Substantial technical and business drivers were identified, which merited the continuous process. The continuous process afforded improved performance and safety relative to batch processes and also improved containment of a highly potent compound.
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