By: Berkeley W. Cue Jr. and Julie B. Manley
The mission of the R&D-based pharmaceutical industry is to discover and develop new medicines that will enable patients to live longer, healthier, and more productive lives. Today, there is a growing realization within the pharmaceutical community that this commitment to health is incomplete without a commitment to a healthy environment. So pharmaceutical scientists are turning to green chemistry to design medicines to continue to be efficacious and high quality, yet with less impact on the environment. Green chemistry is a way of looking at the design of drug molecules and the processes to make them that reduces or eliminates the use and generation of hazardous substances and is achieved by following a set of twelve principles (see Table 1). It is also catching the attention of senior executives who are seeing the “green” ($) in green chemistry.
Green chemistry arose within the U.S. Environmental Protection Agency in the early 1990s as one response to the Pollution Prevention Act of 1990. During the 1990s, there were isolated reports of green chemistry in the pharmaceutical industry but no discernible implementation strategy in any company. Sheldon’s 1992 report on E-factors highlighting that 25–100+ kilograms of waste is generated per kilogram of active pharmaceutical ingredient (API) produced should have catalyzed a more significant effort earlier in the 1990s to design greener processes.
Now it has become more common for pharmaceutical scientists to measure the environmental efficiency, process mass intensity (PMI), of their processes—determining the mass of reactants, process aids, and solvents (including water that contacts the process) used in a synthesis, then dividing by the mass of the product produced. Whatever the metric selected, E-Factor, PMI, life cycle analysis, atom economy, etc., these calculations provide valuable insight on the environmental impact of the process and opportunities for improvement. Many companies including Lilly, AstraZeneca, Merck, and others set internal targets for environmental performance of a process. Why? More than environmental performance is involved; reduced material usage, ambient temperatures, shorter cycle time, higher yield, and reduced waste all save money.
By the early 2000s, some pharmaceutical companies were establishing green chemistry as a strategy to reduce manufacturing waste, starting within the pharmaceutical sciences part of R&D divisions and migrating into manufacturing and drug discovery. In 2005 Pfizer, Lilly, and Merck came together to form the American Chemical Society Green Chemistry Institute Pharmaceutical Roundtable (ACS GCIPR) to address common green chemistry interests and challenges in a precompetitive environment.
Enabling scientists to make informed green chemistry decisions is critical, and as such, the roundtable focuses significant effort to provide scientists with decision-making tools at the bench. PMI calculators, solvent selection guides, and reagent selection guides are just a few.* Although the deliverables are noncompetitive, the manner in which a company chooses to implement them could create a competitive advantage.
Read more about green chemistry practices in the July AAPS Newsmagazine cover story, and let us know the green practices you’re implementing in the comments below.
*Versions of these guides are publicly available here under “Tools.”