The Roundtable advances green chemistry and engineering by forming teams to tackle specific topics of interest to the industry. The implementation of greener practices looks different in each area. Topical areas include:
Roundtable members share their experiences using green analytical tools including UHPLC, supercritical fluid chromatography (SFC), process analytical technologies, in-line reaction monitoring, automation and miniaturization to develop the greenest approach to pharmaceutical problem solving. Members are developing an Analytical Method Greenness calculator to encourage the use of the greenest separation methods. This calculator takes into account key environmental, health and safety aspects associated with analytical instruments and analyses to provide a strong metric for comparing different analytical methods.
Biologics are a growing sector of the pharmaceutical industry and have become a significant portion of many companies’ pipelines. The Roundtable seeks to improve the environmental footprint of biologics development and manufacture through the adaptation and implementation of green chemistry and engineering principles. To this end, the Roundtable developed a Process Mass Intensity (PMI) tool specifically for biologics, which catalogs the amount of water, raw material, and consumable used per kg of product produced. In addition, a Cleaning Mass Intensity(CMI) metric has been developed, that catalogs the amount of water and chemicals used to clean stainless steel equipment. Finally, the Roundtable is working to better understand the current end-of-life practices for single use technology.
Introduction of a process mass intensity metric for biologics
Kristi Budzinski, Megan Blewis, Philip Dahlin, Daniel D’Aquila, Julia Esparza, Jack Gavin, Sa V. Ho, Clarice Hutchens, David Kahn, Stefan G.Koenig, Robert Kottmeier, Jeff Millard, Matt Snyder, Brad Stanard, Lixin Sun. New Biotechnology. 2018. In press, corrected proof. https://doi.org/10.1016/j.nbt.2018.07.005
Special Report: Toward Sustainable Engineering Practices in Biologics Manufacturing
Kristen Brown, Kristi Budzinski, Sa Ho, Jeff Millard, Jeffrey Johnson, Phillip Dahlin, Barbara Owen, and Robert Kottmeier. BioProcess International [Online]; 2015.
The overwhelming majority of bulk active pharmaceutical ingredient manufacturing is accomplished through the use of traditional batch chemical unit operations. Roundtable members have recently organized around a shared desire to promote the development, implementation, and routine use of continuous flow technologies within the Pharmaceutical industry, and to quantify the benefits from a green perspective.
Pharmaceutical Roundtable Study Demonstrates the Value of Continuous Manufacturing in the Design of Greener Processes
Peter Poechlauer, Juan Colberg, Elizabeth Fisher, Michale Jansen, Martin D. Johnson, Stefan G. Koenig, Michael Lawler, Thomas Laporte, Julie Manley, Benjamin Martin, and Ann O’Kearney-McMullan. Org. Process Res. Dev. 2013, 17 (12), 1472-1478. DOI: 10.1021/op400245s
Go with the Flow
Juan Colberg, Stefan Koenig, David Leahy, and Peter Poechlauer. Innovations in Pharmaceutical Technology, 2013, Issue 46, 52-55.
Continuous Processing in the Manufacture of Active Pharmaceutical Ingredients and Finished Dosage Forms: An Industry Perspective
Peter Poechlauer, Julie Manley, Rinus Broxterman, Björn Gregertsen, and Mats Ridemark. Org. Process Res. Dev. 2012, 16 (10), 1586–1590. Publication Date (Web): September 18, 2012 (Concept Article), DOI: 10.1021/op300159y
Greener peptide manufacture is a fast-growing area of interest for the pharmaceutical industry and many companies have invested heavily in developing increased capabilities for peptide synthesis in-house and at contract manufacturing organizations. In recent years, there has been a growing interest in therapeutic peptides within the pharmaceutical industry with more than 50 peptide drugs on the market, approximately 170 in clinical trials, and more than 200 in preclinical development. The synthesis of peptides is associated with the use of comparatively high volumes of hazardous solvent and reagents and little focus on green chemistry and engineering.
In 2016, the ACS Green Chemistry Institute Pharmaceutical Roundtable identified development of greener processes for peptide API as a critical unmet need, and as a result, a new Roundtable team formed to address this important area. In a recent perspective (DOI: 10.1021/acs.joc.8b03001), the greener peptide team summarizes the current challenges of peptide synthesis and purification in terms of sustainability; highlights possible solutions; and encourages synergies between academia, the pharmaceutical industry, and contract research organizations and/or contract manufacturing organizations. This Roundtable team is organizing around benchmarking, sharing best practices, and identifying new synthetic methodologies in an attempt to reduce the environmental impacts associated with these processes.
Roundtable member companies invest heavily in the discovery of new active pharmaceutical ingredients. Key to the success of these efforts are synthetic organic chemists who rapidly develop large libraries of synthetic analogues that are screened for potential activity against a particular disease target. There is an emphasis on the rapid identification of synthetic routes that lead to the isolation of sufficient active ingredient to perform early discovery studies. This emphasis on speed usually results in highly inefficient reaction schemes, isolations and work-ups. By sharing best practices, Roundtable member companies have identified a variety of useful practices to green medicinal chemistry.
Sustainable Practices in Medicinal Chemistry: Current State and Future Directions
Bryan, Marian C.; Dillon, Barry; Hamann, Lawrence G.; Hughes, Gregory J.; Kopach, Michael E.; Peterson, Emily A.; Pourashraf, Meharnez; Raheem, Izzat; Richardson, Paul; Richter, Daniel; Sneddon, Helen. J. Med. Chem. [online early access] DOI: 10.1021/jm400250p. Published Online: April 15, 2013.
Chemistry in Water
There are many who believe that water is the “greenest” solvent, and there has been considerable work in recent years to demonstrate a variety of synthetic reactions in water that historically have only been carried out in organic solvents. Roundtable member companies have organized to share best practices and advance the reaction, work-up, and isolation technology required for running water-based synthetic organic reactions.
Cellulose derivative accelerates organic chemistry in water
June 24, 2018 | C&EN
Historically most catalysis of interest to the Pharmaceutical industry has involved the use of rare platinum group elements like Pd, Pt, Ru, Rh, Ir, etc. Recent work has demonstrated many key catalytic coupling reactions that have been carried out with these precious metals using earth abundant metals like Fe, Ni, Co to carry out some catalysis, but this has had limited success and applicability. Arguably, the future of catalysis in the Pharmaceutical industry is to be found in biocatalysis. Recent work in directed evolution and molecular engineering have enabled the development of asymmetric chiral coupling reactions and other catalytic reactions that far exceed the capabilities of transition metal catalysts, don’t involve the use of rare metals, and are far greener from multiple perspectives. Roundtable member companies have organized to share best practices and advance biocatalytic technology.