Life cycle thinking

Application of LCA and Green Chemistry metrics to API manufacturing

The relationship between Green Chemistry and LCA is well established, and some attempts have been made to combine Green Chemistry metrics and LCA (Lokesh et al., 2020; Blömer et al., 2024). Fundamentally, Green Chemistry considers material (and energy) inputs, and the hazards posed by these materials, within processes, while LCA evaluates the withdrawals from/emissions into the environment made by those processes (Blömer et al., 2024). A simple and complementary approach is to use the Process Mass Intensity (PMI) metric in combination with LCA midpoint indicators (Cespi et al., 2015). For example, a comparison between two ways to produce sildenafil citrate, the active pharmaceutical ingredient (API) of Viagra™, has been made. The manufacturing process is more efficient than the original small scale drug discovery route, with PMI more than halved (from 80 to 33) and across the board reductions in midpoint indicators (Cespi et al., 2015). Much of the waste and emissions savings come from reducing solvent volumes and changing the purification from chromatographic separations to recrystallisation. Some safer reagents are also employed but improved yield is also important because Green Chemistry metrics are typically normalised by the mass of product, and likewise LCA functional units are often the mass of product or a property proportional to mass (e.g. 1 daily dose of medicine).