“The ACS GCIPR has defined and implemented a process mass intensity metric for measuring material resource efficiency of manufacturing routes to active pharmaceutical ingredients,” because “the total volume of solvent used is also an important measure,” noted Caireen Hargreaves, senior environmental specialist, AstraZeneca.
As Quirinus B. Broxterman, Ph.D., corporate scientist for route scouting and selection at DSM recalled, “When Roundtable members reported their PMIs in 2008, more than half was solvent use, and nearly one-third was water. Most of that occurs in the preclinical phase, as chemists do everything possible to make the compound.” PMI decreases significantly once the compound is in clinical development.
PMI and E-factor are the two leading mass-based quantitative options, but PMI is a better indicator of sustainability than the E-factor equation, Dr. Broxterman said. “PMI relates to kilograms of product you make and, therefore, easily captures the interest of the nonscientific aspects of a company.” The use of PMI also allows the easy transition to carbon footprint measurement.
The Roundtable is rolling out a simple PMI calculator with calculations embedded in a spreadsheet, so users only need enter the quantities of reagents, solvents, and water. “To facilitate more sustainable manufacturing, we need to quantify relevant sustainability parameters. PMI is a first-generation parameter and is a good (starting point) to drive toward a carbon footprint, an ecofootprint, or something to be defined,” Dr. Broxterman concluded.
Solvent Selection Guide
ACS GCIPR introduced its solvent selection guide recently, based upon safety, health, and environmental parameters. “Because effectiveness of a solvent for a particular reaction or work-up step depends upon the chemistry and conditions used, the effectiveness of the solvent was not included in the scope of this work,” Hargreaves said.
The PDF version of the guide is available at www.acs.org/gcipharmaroundtable, and as an iPhone app. The guide may be used to “compare solvents scored in the Roundtable guide to those of their own corporate guides, and to raise awareness and provide a resource.”
“By switching to green solvents, a company can expect equivalent functional and performance with minimized environmental impact.”
Green chemistry also may lower waste disposal costs for harmful solvents, reduce the need for expensive emissions abatement equipment, and lower the costs of virgin solvent when solvents can be recycled. Other speakers added greater efficiency and reduced energy use to green chemistry’s attributes.
But, there are tradeoffs, Hargreaves acknowledged. “Some newer alternatives may still be limited in production scale and the number of available suppliers, and some common laboratory reagents may not be readily available in the new alternative solvents.”
Additionally, there are data gaps for some green solutions, making it difficult to fully assess them against the Roundtable solvent selection guide. “Regulatory guidance is not yet in place for some of the newer alternatives,” she added.