Scale-up for Dummies
Member of Chimica Oggi – Chemistry Today’s Scientific Advisory Board
When I started as a young chemist in process development, I felt well prepared for my job in early phase development and rapid scale-up – but can you learn scale-up from books or do you have to learn it from experience and mistakes? One of my first projects contained a step which involved a hydroboration followed by a quench with hydrogen peroxide. In laboratory this reaction, while strongly exothermic, performed extremely well, therefore we felt confident scaling up to 600 L vessel size. Everything performed as expected until the technician went for lunch and asked me to control the quench with hydrogen peroxide. When I observed that the reaction was well below the upper temperature limit, I thought: ok, let´s speed this up! So I slightly increased the addition rate as I would have done as if still working in the lab. Things did not go as I expected. The slightly increased addition rate resulted in a rapid temperature rise. I quickly stopped dosing to prevent the reaction from overheating but we lost quite some time until the reaction was cooled down and we could re-start dosing again. Of course I learned before that heat transfer pro volume decreased with increas ...