Our latest blog series is designed to guide readers towards a greener, more sustainable laboratory [environment]. In 1998, Paul Anastas and John Warner defined the 12 principles of Green Chemistry in their book, Green Chemistry: Theory and Practice.1 Yale Professor Paul Anastas, also known as the “father of Green Chemistry,” defined the specific tenets required to achieve more sustainable chemistry processes. Each blog entry will be devoted to one principle in sequential order.
First Principle: Prevent Waste
This first principle states that a chemist must “Design chemical syntheses to prevent waste. Leave no waste to treat or clean up.” As Berkeley W. Cue, Jr., Ph.D., of BWC Pharma Consulting, LLC, has interpreted: “It is better to prevent waste than to treat or clean up waste after it has been created.”2 This principle should take precedence over all other principles of green chemistry and that the other eleven are only ways to achieve the first one.
Of course, one critical question beyond all the apparent safety, health, and ecological concerns: why prevent waste? As Michael Kopach from Eli Lilly shared in his presentation, “The Business Case for Green Chemistry,” at the TIDES conference last year, the volume of waste generated in traditional peptide synthesis and what that equates to in dollars spent just to deal with it is astounding! Kopach references B.W. Cue’s and Wei Zhang’s book, which addresses these issues.3,4 In another article, this one quoting Jan Pawlas, Ph.D., a scientist in global development at the PolyPeptide Group, says, “The current (traditional solid-phase peptide synthesis) methods can produce any peptide at scale, but have a big impact on the environment. Producing one kilogram of the GLP-1 agonist exenatide generates up to 34 tons of waste and 118 tons of carbon dioxide.”5 That waste in its original form has a cost, along with a steep price associated with its removal.
One way to measure waste prevention is by a formula called the “E-Factor.” As the creator of the E-Factor, Roger A. Sheldon, a recognized authority in green chemistry, asserts in his paper “The E-Factor: Fifteen Years On,” “We conclude that the E-Factor concept has played a major role in focusing the attention of the chemical industry worldwide, and particularly the pharmaceutical industry, on the problem of waste generation in chemicals manufacture.”6 Simply stated, the E-Factor is E=kg waste/kg product.
One way to reduce the E-factor is to implement recycling strategies as part of the process from the start, as Dr. K. Mihlbachler from Repligen and Dr. O. Dapremont from SK pharmteco Small Molecules US stated in Chapter 22 of the 2012 edition of the W. Zhang and B. W. Cue book.7 Preparative chromatography, a well-known technique for purification, is unfortunately also considered expensive due to the massive amounts of solvent consumed in the process. However, a well-optimized chromatography process combined with solvent recycling can be surprisingly effective and environmentally friendly. For example, the authors highlighted how commercial-scale chiral separations using a Simulated Moving Bed (SMB) resulted in an E factor 10 times smaller than the competing tartaric resolution thanks to recycling the solvent and the undesired enantiomer via racemization.
However, a new calculation has gained favor with the American Chemical Society in recent years. The paper, “Using the Right Green Yardstick: Why Process Mass Intensity Is Used in the Pharmaceutical Industry to Drive More Sustainable Processes,” declares in the abstract: “There have been many publications and much discussion about green metrics. While many have been proposed, The American Chemical Society Green Chemistry Institute’s Pharmaceutical Roundtable has chosen Process Mass Intensity (PMI) as the key, high-level metric for evaluating and benchmarking progress towards more sustainable manufacturing.”8,9
This metric means optimizing production processes to minimize byproducts or waste materials. Better optimization, new technologies, and recycling strategies make this easily applicable in the small molecule space but less obvious in Cell and Gene therapy.10
This entry details some of the advantages and drawbacks of both metrics. For those wanting more details of PMI, you can find a link to the ACS’s PMI Tool here.
For non-hazardous waste, SK pharmteco has instituted the following:
- In Ireland, ZERO waste goes to landfill.
- At our Korean facilities, there is a 95% diversion rate with other facilities, ensuring that 100% of non-hazardous waste goes through a recovery process.
- At our US facilities, solvent recycling strategies are developed as part of the process.
Many other valuable resources listed below can assist you with adhering to this “First Principle.”
References
- P.T. Anastas, J.C. Warner, Green Chemistry: Theory and Practice, Oxford University Press (1998).
- https://www.acs.org/content/acs/en/greenchemistry/principles/12-principles-of-green-chemistry.html
- M. Kopach, The Business Case for Green Chemistry (presentation) (2020).
- W. Zhang, B.W. Cue, Green Techniques for Organic Synthesis and Medicinal Chemistry, John Wiley & Sons (2018).
- https://www.biospace.com/article/tides-polypeptide-group-outlines-cost-effective-green-methods-for-peptide-synthesis/
- R.A. Sheldon, Green Chem., 9, 1273 (2007).
- Kathleen Mihlbachler, Olivier Dapremont, Chapter 22 Preparative Chromatography in W. Zhang, B.W. Cue, Green Techniques for Organic Synthesis and Medicinal Chemistry, John Wiley & Sons (2012).
- C. Jimenez-Gonzalez, C.S. Ponder, Q.B. Broxterman, and J.B. Manley, Org. Process Res. Dev., 15 (4), 912 (2011).
- D. J. C. Constable, A. D. Curzons and V. L. Cunningham, Green Chem., 4, 521 (2002).
- R.A. Sheldon, Green Chem., 19, 18 (2017).
