The production of increasingly complex molecules is associated with considerable environmental impacts. Novel approaches to process development can lead to better performance without compromising product quality.
Medicines manufacturing faces growing challenges due to the extensive reliance on organic solvents in standard processes. The industry is noted for its poor process mass intensity (PMI), which measures the amount of waste per unit of active pharmaceutical ingredient (API) produced. This can range from values of about 10 for small molecule drugs, to 15,000 for emerging therapies such as oligonucleotides. In addition to this poor material efficiency, the heavy reliance on solvent swaps leads to high energy consumption. The current approach also limits the resilience of the industry to external changes is also, e.g., due to shortfalls in the supply of acetonitrile or to new regulations that restrict the set of allowable solvents.
Sargent Centre researchers are finding new ways to make medicines manufacturing safe and sustainable by enabling a holistic end-to-end approach to process development, helping industry practitioners make sustainable decisions from the initial stages of route selection. They focus on the most pressing problems by collaborating with pharmaceutical companies, e.g., through a large-scale Prosperity Partnership with Eli Lilly and Company or through active engagement in the CMAC consortium.
One of the strategies used by Sargent Centre researchers is to incorporate sustainability-related constraints within model-based design and to take into account multiple key performance indicators as objectives within the methodologies developed, including cost, environment and safety. Discussions with partners and stakeholders serve to identify appropriate metrics for process development, such as safety and environmental indicators, E-factors, energy consumption. Because solvents are a major source of environmental and safety impacts for the pharmaceutical industry, the approaches developed support early decision-making (e.g., route selection, solvent selection for individual process units) as well as whole-system modelling. This approach has been found to lead to significant reductions in solvent use, energy consumption and potential impacts when applied to the production of mefenamic acid, ibuprofen and peptide production
Sargent Centre researchers are actively working to make a positive social impact by accelerating process development through quality by digital design. Indeed, the deployment of systems-based approaches can reduce the time needed for new therapies to reach patients and to lower the cost of medicines through reduced R&D and manufacturing costs.
