On scaling up, various scenarios can negatively affect product quality and the demand for raw materials, versus the lab version of a process. This has a knock-on effect on the environmental footprint of the process.[1-3] For example, the selectivity of a reaction with very fast solution kinetics will change, often for the worse, without careful consideration of the effect of changing scale or equipment. Likewise, limits in the ability to add or remove heat from batch processing equipment, on scaling up, can extend the duration of operations versus the lab. Overcoming these challenges requires process engineers. In brief, they establish a process can be accommodated in a facility so as to meet expectations around quality, manufacturability or process safety. Where risks to any of them cannot be eliminated, process engineers will work to mitigate them, increasingly using modelling and simulation to predict outcomes to various scenarios, without physically executing large numbers of laboratory experiments.
On top of these are some additional principles taken from the Sandestin Declaration::
It should be clear from the above principles that process engineers have a remit to select equipment or processing methods that will drive down cycle time, energy consumption and waste.[6-7] This is underpinned by understanding of internal mass and energy flows, consideration of opportunities to give each molecule the same processing experience, and a desire to optimize the forces driving reactivity, selectivity and separation at every scale. As part of its integration with chemistry, it is important to adopt a lifecycle mindset, with the consideration of the upstream and downstream impact of a particular solution.
A focus for these “intensification” efforts is often separation operations. For every two reactions, approximately two extractions, one distillation, one crystallisation, one product isolation, and one product drying step are performed, on top of filtration operations to remove decolourizing carbon or extraneous solids. These separation steps contribute a range of 40-90% of the cumulative process mass intensity. Distillation and drying steps alone often consume more than 50% of the energy requirements of a process, while additionally acting as bottlenecks to increases in productivity. It can be challenging to recover high quality solvent from a waste stream containing mixtures of solvents through distillation, forcing its incineration.
For both reactive chemistry and separations, novel, less energy intensive methods that can process a large continuous flow of material with a short residence time are required to drive a step change in energy consumption, solvent utilization and the amount of waste generated when manufacturing pharmaceuticals.[9-10] Continuous processing reduces the dependency on the characteristics of a fixed plant, and to engineer characteristics of the processing equipment around the needs of the chemistry. For example, the superior heat removal characteristics of continuous reactors allow them to provide an alternative to performing cryogenic chemistry in batch. Depending on the temperature involved, cryogenic chemistry can limit the batch size, be difficult to control and make a marked impact on cycle time, as well as being subject to higher levels of mixing-related impurities compared to a flow chemistry equivalent. Investment in these and other opportunities is hindered by the domination of manufacturing plant equipment by multipurpose equipment that is fixed in nature.
By the end of this module you should: