cGMP Manufacturing Aspects of API Continuous Cooling and Antisolvent Crystallization for Kinetic Impurity Rejection

Time: 9:00 am
day: Day Two


• Plant throughput kg/h was 200X larger than development scale. Run time in the
plant was 7X longer than in development. There was no startup transition waste
for the continuous evaporation, crystallization, and semi-continuous filtration
sections. Stop/restart was done 17 times with no diverting to waste
• Surge drums decoupled the upstream chemistry CM sections from the continuous
crystallization, which served to allow one section of the flow train to keep
running while the other section was down
• Broad RTD dampened out disturbances, and this fact was used in the divert
decisions. RTD numerical modeling was used, and necessary, for calculating lot
genealogy for all batches
• Cleaning frequency was adjustable. In this campaign, it was left to the judgment
of the cGMP operations and technical staff to decide when it was time to stop for a
cleanout, rather than specifying a fixed time duration – In general, it is best to keep
cleaning frequency adjustable rather than specify and validate a specific time