Introduction to Process Engineering
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.
Analogous to the Twelve Principles of Green Chemistry, there are Twelve Principles of Green Engineering.[4] These are:
- Materials and energy inputs and outputs should be designed to be as inherently nonhazardous as possible.
- It is better to prevent waste than to treat or clean up waste after it is formed.
- Separation and purification operations should be designed to minimize energy consumption and materials use.
- Products, processes and systems should be designed to maximize mass, energy, space, and time efficiency.
- Products, processes, and systems should be “output pulled” rather than “input pushed” through the use of energy and materials.
- Embedded entropy and complexity must be viewed as an investment when making design choices on recycle, reuse, or beneficial disposition.
- Targeted durability, not immortality, should be a design goal.
- Avoid solutions that provide unnecessary capacity or capability.
- Material diversity in multicomponent products should be minimized to promote disassembly and value retention.
- Design of products, processes, and systems must include integration and interconnectivity with available energy and materials flows.
- Products, processes, and systems should be designed for performance in a commercial “afterlife”.
- Material and energy inputs should be renewable rather than depleting.
On top of these are some additional principles taken from the Sandestin Declaration:[5]:
- Conserve and improve natural ecosystems while protecting human health and well-being.
- Use lifecycle thinking in all engineering activities.
- Develop and apply engineering solutions, while being cognizant of local geography, aspirations, and cultures.
- Create engineering solutions beyond current or dominant technologies; improve, innovate, and invent (technologies) to achieve sustainability.
- Actively engage communities and stakeholders in development of engineering solutions.
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.[8]
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.[11] 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.[12]
Learning Objectives:
By the end of this module you should:
- Understand why a small-scale process cannot typically be scaled up directly;
- Be aware of the problems that can occur during the scale up of a catalytic reaction.
- C. P. Jiménez‐González, C. S. Ponder, R. E. Hannah and J. R. Hagan, Green Techniques for Organic Synthesis and Medicinal Chemistry, ed. W. Zhang and B. W. Cue Jr., John Wiley & Sons, 2012, ch. 27, pp 701-714.
- C. P. Jiménez‐González, C. S. Ponder, R. E. Hannah and J. R. Hagan, Chemical Engineering in the Pharmaceutical Industry, D. J. am Ende, John Wiley & Sons, 2010, ch. 4, pp 57-65.
- C. L. Kitchens and L. Soh, Green Engineering, in Green Techniques for Organic Synthesis and Medicinal Chemistry. W. Zhang and B. W. Cue Jr, John Wiley & Sons, second edn., 2018.
- P. T. Anastas and J. B. Zimmerman, Peer Reviewed: Design Through the 12 Principles of Green Engineering, Environ. Sci. Technol. 2003, 37, 94A–101A.
- M. A. Abraham and N. Nguyen, , “Green engineering: Defining the principles”— resdts from the sandestin conference, Environ. Prog., 2003, 22, 233–236.
- C. Jiménez-González, P. Poechlauer, Q. B. Broxterman, B-S. Yang, D. am Ende, J. Baird, C. Bertsch, R. E. Hannah, P. Dell’Orco, H. Noorman, S. Yee, R. Reintjens, A. Wells, V. Massonneau and J. Manley, Key Green Engineering Research Areas for Sustainable Manufacturing: A Perspective from Pharmaceutical and Fine Chemicals Manufacturers, Org. Process Res. Dev., 2011, 15, 900–911.
- J. B. Zimmerman, P. T. Anastas, H. C. Erythropel and W. Leitner, Designing for a green chemistry future, Science, 2020, 367, 397-400.
- ) F. L. Muller, Chimica Oggi, 2013, 31, 34-38.
- Sustainable Separation Processes: A Road Map to Accelerate Industrial Application of Less Energy-Intensive Alternative Separations (AltSep),, (accessed August 2023).
- J.-C. Charpentier, What Kind of Modern “Green” Chemical Engineering is Required for the Design of the “Factory of Future”?, Procedia Eng., 2016, 138, 445-458.
- S. G. Newman and K. F. Jensen, The role of flow in green chemistry and engineering, Green Chem., 2013, 15, 1456-1472.
- D. Patel, S. Kellici and B. Saha, Green Process Engineering as the Key to Future Processes, Processes, 2014, 2(1), 311-332.
- Route Selection
- GMP
- Introduction to Process Engineering
- Route Selection and Scale Up: Case Study and Exercise
- Process Safety
- Reactive Hazards in Scaling Up: Case Study and Exercise
- Design of Experiments
- Some Definitions
- The Experimental Design Process
- Comparing Traditional Approaches to Experimental Design
- Examples of Variables and Responses for a Chemical Process
- Main Effects and Interactions
- Experimental Designs: Factorial Designs
- Experimental Designs: Response Surface Design
- Design of Experiments: Summary and Further Reading
- Reaction Work-up and Product Isolation
- Environmental Legislation
- Abatement and Waste Treatment