ACS GCI Pharmaceutical Roundtable: 20 years of green chemistry leadership (73)

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Three founding members, Pfizer, Lilly, and Merck, were joined by four more companies within a year. Initial projects included benchmarking green chemistry practices, identifying top chemistry challenges, publishing green chemistry case studies, and strategizing how to bring green chemistry into earlier phases of the R&D process.

 

As the Roundtable developed, they identified the following strategic objectives—which have guided them until today: 1) Informing and Influencing the Research Agenda, 2) Defining and Delivering Tools for Innovation, 3) Educating Students & Influencing Leaders, and doing all of these while collaborating globally.

 

In 2018 in response to interest and changes in the industry, the Roundtable updated its business plan to open the door up to companies in the supply chain, including CDMOs, as associate members, and companies in related industries (e.g., agrichemicals and animal health) as affiliate members. As a result, membership has grown dramatically to over 50 companies today (Figure 1); with 11 companies from Asia, 19 from Europe and 20 from the U.S. The diversity of voices at the table brings a strength to the Roundtables projects.

 

Metrics & Tools

 

Green chemistry and green engineering are more of a journey than a destination; with innovations driving improvements. Therefore, it is critical to be able to measure improvements, and to identify the best reactants, solvents, and processes to use that result in improved sustainability. The ACS GCIPR has put significant effort into defining metrics and creating tools to help identify and predict greener reactants, solvents, and routes. Their tools are vetted by members and made freely available on the Roundtable website.

 

Process Mass Intensity & Life Cycle Analysis. Various metrics have been proposed over the years to measure green chemistry improvements. From the beginning, the ACS GCIPR selected Process Mass Intensity (PMI) to streamline benchmarking exercises and focus attention on areas where improvements could have the biggest impact. PMI measures the total amount of mass, including solvents and water, in making a quantity of final product. To help benchmark PMI, the Roundtable created a PMI Calculator, and subsequently a Convergent PMI Calculator to handle convergent synthesis. (1) Over time, the desire to incorporate life cycle considerations into PMI metrics arose, leading to the development of a PMI Life Cycle Analysis (LCA) calculator. The PMI LCA tool employs data from ecoinvent to provide a high-level estimate of PMI and environmental life cycle information for a wide range of processes for small molecule synthesis. (2) (Figure 2).

 

Solvents. In 2006 the ACS GCIPR conducted their first PMI benchmarking exercise which clearly identified solvents as the most significant impact on the PMI of Active Pharmaceutical Ingredient (API) synthesis. (3) Based on this, selecting better solvents and reducing overall solvent use became a GCIPR priority.

 

First, they coalesced several solvent guides used by member companies into one standard guide later. This was later updated by the EU-funded Chem21 initiative, and currently is available on the Roundtable’s GChELP website. (4) Subsequently, they released the Solvent Selection Tool, which allows users to search for solvents based on the desired physical properties, and then filter based on Safety, Health, and Environmental (SHE) data. (5, 6).

 

Reagents. Reagent selection is another area the Roundtable has tackled by producing a series of guides that provide a wealth of information on reagent options within different transformations. There are 27 guides to date with hundreds of reagents catalogued. Each guide provides a mechanistic overview with literature references, and includes scale up examples, a green review, and a visual display employing a Venn diagram to depict the reagents relative placement among three factors—utility, scale up, and greenness. (Figure 2) (7).

 

Acids and Bases. Similar to the Solvent Selection Tool, this interactive tool allows for selection of more sustainable acids and bases.

Users can filter over 200 acids and bases by parameters such as functional groups, melting points, and boiling point, and then review the SHE data points. (Figure 3) (8).

 

Predictive Tools. From the beginning, the ACS GCIPR has sought to integrate green chemistry into discovery, so that processes are developed as green as they can be from the beginning. Predictive tools would allow chemists to identify the greenest routes from a selection of potential processes. The PMI Prediction Calculator uses historical data from Roundtable member companies and literature to predict a PMI for a proposed step or multi-step route (9).

 

Specialty Tools. The Analytical Chemistry Greenness Score (AMGS) tool provides a metric to enable the comparison between separations methods used in drug development and has been widely adopted by analytical chemists. (10) Another tool, the iGAL 2.0 Scorecard, calculates a greenness score for your API process based on pharma benchmarks. (11) Other tools developed by the Roundtable, include a) the Biocatalysis Guide, a quick reference for the most employed enzyme classes, b) Med Chem Tips and Tricks for greener medicinal chemistry, and c) the BioPharma PMI Calculator which measures the mass efficiency of producing biologic drug substances using tailored inputs including water, raw materials, and consumables. (12, 13, 14).

 

Research Grants

Partnerships between industry and academia are fruitful in driving innovation in green chemistry technologies that have the most chance of being adopted by industry and resulting in real world sustainability impact. In 2007, the ACS GCIPR published their first paper identifying key green chemistry research areas (15) and launched a grant program to begin to fund academic research within these areas. To the ACS GCIPR grant program has distributed over $4.3 million in funds. The Roundtable updated their key research paper in 2018 (16).

Academic collaborators work closely with a designated contact on the Roundtable to provide feedback during the research term. This collaboration has been fruitful for professors and especially for graduate students involved. Students and professors often have the opportunity to present research in symposia organized by the Roundtable after their results are final. In 2017, a review of the grant program’s first 10 years included 28 funded projects with 73 primary papers and 1700 unique daughter citations. (17) A review of the second decade of funding is being conducted. To date there have been more than 75 grants awarded.

 

In addition to funding key research areas, the Roundtable has run a successful Ignition Grant program for high-risk, new research directions relevant to any aspect of greener pharmaceutical chemistries or processes. In 2024, the Ignition grants were $40,000 USD 6-month grants, whereas the key research grants were $80,000 USD 12-month grants.

Education & Awards

 

Training the next generation of scientists and providing opportunities for current professionals to gain green chemistry skills has been a key objective of the Roundtable from the beginning. The Roundtable is actively engaged in putting together symposia and workshops at chemistry conferences globally. The Roundtable also publishes a summary of articles of interest to the pharmaceutical industry twice a year.
In 2025, the ACS GCIPR will be hosting a series of events in the U.K., U.S., and virtually in celebration of their 20th anniversary (18).

 

The Green Chemistry and Engineering Learning Platform (GChELP) is an online e-course that provides interactive modules on sustainable methodologies used in the synthesis of pharmaceuticals. (Figure 4) (19) The platform is the evolution of the Chem21 training program developed from the Innovative Medicines Initiative with funding from the European Union. The GChELP modules cover foundational principles, solvent and reagent guides, metrics, greener methodologies such as biocatalysis, flow chemistry, etc.), process design, and life cycle considerations. The GChELP modules can be taken out-of-order and therefore selected to fill in areas relevant to the learner. In this way, companies are using GChELP as an onboarding tool for new hires to get them familiar with areas typically not covered in chemistry education.
Another aspect of the Roundtable’s outreach efforts involves their awards program to recognize excellence in greener pharmaceutical implementation. The Roundtable now has four awards including an award for CMOs, an award for AI and Data Science, and their newest award for Discovery Chemistry. (20) Award winners are highlighted at the ACS GCI’s annual Green Chemistry & Engineering Conference in an awards symposium. These case studies provide value in influencing and motivating industry in their pursuit of sustainable technologies, as well as learning examples for students.

 

Roadmap to 2045

 

As the ACS GCIPR looks forward to the next 20 years, we will be defining a road map to continue advancing our mission – to catalyze green chemistry and engineering in the pharmaceutical industry. We will be looking at new tools and metrics that would enable chemists to quantify the impact of greener technology, better leverage data-powered predictive tools, and incorporate holistic, life cycle thinking into process design. New research areas continue to develop, with more attention on large molecule synthesis in addition to small molecule synthesis. Finally, stronger collaboration throughout the value chain will enable green chemistry to power the global industry.

 

Figure 1. Location of Roundtable members headquarters as of January 2025. Blue pins are members, yellow pins are associate members, and teal pins are affiliate members.

Figure 3. Venn diagram for reagent guides showing placement of ideal reagents within overlapping areas of Wide Utility, Scalability, and Greenness.

 

Figure 4. GChELP modules.

 

References and notes

1. Process Mass Intensity (PMI) – ACSGCIPR [Internet]. Acsgcipr.org. 2025 [cited 2025 Jan 27]. Available from: https://acsgcipr.org/tools/process-mass-intensity/
2. PMI Life Cycle Assessment – ACSGCIPR [Internet]. Acsgcipr.org. 2025 [cited 2025 Jan 27]. Available from: https://acsgcipr.org/tools/pmi-life-cycle-assessment/
3. Jimenez-Gonzalez C, Ponder CS, Broxterman QB, Manley JB. Using the Right Green Yardstick: Why Process Mass Intensity Is Used in the Pharmaceutical Industry To Drive More Sustainable Processes. Organic Process Research & Development. 2011 Jul 15;15(4):912–7.
4. ‌Solvent Tool – ACSGCIPR [Internet]. Acsgcipr.org. 2025 [cited 2025 Jan 27]. Available from: https://acsgcipr.org/tools/solvent-tool/
5. The CHEM21 Solvent Selection Guide – ACS GCI Pharmaceutical Roundtable [Internet]. Acsgcipr.org. 2016 [cited 2025 Jan 27]. Available from: https://learning.acsgcipr.org/guides-and-metrics/solvent-selection-guides/the-chem21-solvent-selection-guide
6. ‌Prat D, Wells A, Hayler J, Sneddon H, McElroy CR, Abou-Shehada S, et al. CHEM21 selection guide of classical- and less classical-solvents. Green Chemistry. 2016;18(1):288–96.
7. Reagent Guides [Internet]. Acsgcipr.org. 2025 [cited 2025 Jan 27]. Available from: https://reagents.acsgcipr.org
8. ‌Acid-Base Selection Tool – ACSGCIPR [Internet]. Acsgcipr.org. 2025 [cited 2025 Jan 27]. Available from: https://acsgcipr.org/acid-base-selection-tool
9. ‌Process Mass Intensity Prediction Calculator – ACSGCIPR [Internet]. Acsgcipr.org. 2025 [cited 2025 Jan 27]. Available from: https://acsgcipr.org/tools/process-mass-intensity-prediction-calculator/
10. AMGS Spreadsheet [Internet]. Acsgcipr.org. 2025 [cited 2025 Jan 27]. Available from: https://acsgcipr.org/amgs
11. ‌iGAL 2.0 Scorecard Calculator – ACSGCIPR [Internet]. Acsgcipr.org. 2025 [cited 2025 Jan 27]. Available from: https://acsgcipr.org/tools/igal-2-0-scorecard-calculator/
12.  Biocatalysis Guide [Internet]. Acsgcipr.org. 2025 [cited 2025 Jan 27]. Available from: https://acsgcipr.org/tools/biocatalysis-guide/
13. ‌MedChem Tips and Tricks – ACSGCIPR [Internet]. Acsgcipr.org. 2025 [cited 2025 Jan 27]. Available from: https://acsgcipr.org/tools-for-innovation-in-chemistry/medchem-tips-and-tricks
14. ‌Biopharma PMI Calculator – ACSGCIPR [Internet]. Acsgcipr.org. 2025 [cited 2025 Jan 27]. Available from: https://acsgcipr.org/biopharma-pmi-calculator/
15. ‌Constable DJC, Dunn PJ, Hayler JD, Humphrey GR, Leazer, Jr. JL, Linderman RJ, et al. Key green chemistry research areas—a perspective from pharmaceutical manufacturers. Green Chem. 2007;9(5):411–20.
16. Bryan MC, Dunn PJ, Entwistle D, Gallou F, Koenig SG, Hayler JD, et al. Key Green Chemistry research areas from a pharmaceutical manufacturers’ perspective revisited. Green Chemistry. 2018;20(22):5082–103.
17. ‌Koenig SG, Leahy DK, Wells AS. Evaluating the Impact of a Decade of Funding from the Green Chemistry Institute Pharmaceutical Roundtable. Organic Process Research & Development. 2018 Sep 20;22(10):1344–59.
18. ‌Events – ACSGCIPR [Internet]. Acsgcipr.org. 2025 [cited 2025 Jan 27]. Available from: https://acsgcipr.org/learning/events/
19. ‌ACS GCI Pharmaceutical Roundtable – Learning [Internet]. Acsgcipr.org. 2025 [cited 2025 Jan 27]. Available from: https://learning.acsgcipr.org/
20. Industry Awards – ACSGCIPR [Internet]. Acsgcipr.org. 2025 [cited 2025 Jan 27]. Available from: https://acsgcipr.org/funding-awards/industry-awards/