Safety by Design: Making Bigger, Better

Joe Willmot shares the methodologies and data required to achieve a robust and safe scaleup from lab to manufacture

THERE’S no avoiding it; chemical reactions and the products they create, such as polymers and active pharmaceutical ingredients (APIs), are central to our world. Creating these modern essentials can be a hazardous business that, unfortunately, may have fatal consequences when things go wrong. One of the most significant challenges for process safety happens when a chemical compound’s production scales up, moving beyond lab-based synthesis to pilot plant and finally into full-scale manufacture.

There are vast chemical, physical, and operational differences between small, lab-based, chemical reactions and those taking place in large-scale operations. These differences represent the main challenges of process scaleup. Most of the risks associated with scaling up processes come through changes in heat-loss behaviour. Whole sections of government documentation are dedicated to helping identify and mitigate these risks, such as the HSE’s Designing and Operating Safe Chemical Reaction Processes. These changes can then cause secondary effects, such as unwanted pressure generation or thermal runaway of a reaction. When volumes differ, physical behaviours change.

Here’s the basis of the scaleup challenge: volume increases at a quicker rate than surface area does. Cooling through surface temperature losses at the lab scale is not replicated at a large scale. A simple example of this effect is the difference in the volume:surface-area ratio between cubes of 1 cm³ volume and 1 m³ volume.