Chapter 17. Industrial Continuous-flow Chemistry under cGMP Conditions

Adopting continuous manufacturing requires considerable upfront investment in technology and expertise to develop and execute robust processes. cGMP manufacturing control strategies for drug substance processes in particular are limited, with few real case studies available in the literature. Making the change from a traditional batch manufacturing paradigm to a new continuous paradigm can be highly disruptive. In this chapter, key enablers for running continuous processes including multi-step processes are presented. These enablers allow the process to run in a state of control such that the environmental, safety, quality and cost benefits associated with continuous processing may be realized. The enablers include the use of process analytical technology, a material tracking system, a diversion strategy and the incorporation of surge capacity. Examples from the field where these control strategy enablers were successfully used to produce drug substance API using continuous technology under cGMP conditions are also presented. In these case studies the environmental, safety and quality benefits realized are highlighted and the evolution of the technology from single step batch-continuous hybrid processes to multi-step fully continuous telescoped processes is described.