416384 Multi-Step Continuous GMP Production of a Highly Potent Compound

Tuesday, November 10, 2015: 10:10 AM
Ballroom B (Salt Palace Convention Center)
Jennifer M. Groh, Kevin P. Cole, Bradley M. Campbell, Martin D. Johnson, Neil Kallman, David Mitchell and Christopher S. Polster, Small Molecule Design and Development, Eli Lilly and Company, Indianapolis, IN

The development of a GMP continuous process to synthesize a highly potent compound is disclosed.  A dedicated, inexpensive equipment set run in laboratory fume hoods was utilized on manufacturing scale with in-process monitoring.  This process included four unit operations including a continuous crystallization and filtration.  Two chemical reactions were run plug flow tube reactors.  One of these PFRs was designed to strip off a gas byproduct continuously during reaction and decouple liquid residence time from gas residence time.  Continuous anti-solvent driven crystallization was done using two MSMPRs in series.  Continuous filtration, washing, drying, and re-dissolving eliminated the isolation of a potent intermediate.  Throughput was 4 kg per day in-situ penultimate from the GMP manufacturing plant.  Finally, the robustness of the process and a comparison of lab and commercial scales highlighting the challenges that were encountered will be discussed.

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