(626d) System-Model Development for Continuous Drug Substance Manufacturing Process

Continuous manufacture (CM) of small molecule drug substance offers several advantages over traditional batch processes, especially when the chemistry is very complex and/or process requires fine control of process conditions. The advantages of CM have been highlighted elsewhere [1, 2], and as demonstrated and noted by these authors, precise understanding of system dynamics via system/process modeling and/or residence time distributions is crucial in CM.

In this presentation, GlaxoSmithKline’s CM process and system model development approach will be discussed for an asset which utilizes three continuous drug substance unit operations. The focus will be on biphasic reaction and continuous evaporator models. System-level understanding via global sensitivity analysis and model’s usage in various stages of process development will be discussed.

References

[1] Cole et al., 2017, Science, 356(6343), 1144-1150.

[2] Lee et al., 2015, J. Pharm. Innov., 10, 191-199.