(267e) Multi-Step Continuous GMP Production of a Highly Potent Compound
- Conference: AIChE Annual Meeting
- Year: 2015
- Proceeding: 2015 AIChE Annual Meeting Proceedings
- Group: Pharmaceutical Discovery, Development and Manufacturing Forum
- Time: Tuesday, November 10, 2015 - 10:10am-10:35am
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.