Multi-Step Continuous GMP Production of a Highly Potent Compound

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.