By Cecilia Smith, Administrative Assistant, ACS Green Chemistry Institute
Amid changing regulatory landscapes and increased need for industrial scale sustainability practices, metrics tracking the environmental and health impacts of chemicals and processes are crucial for improving efficiency, spurring sustainable innovations, and raising awareness of best practices. Developing these tools and metrics is a strategic priority of the ACS GCI Pharmaceutical Roundtable (GCIPR), and on the occasion of its 20th anniversary, it is dedicating resources to move three projects forward that will develop and/or evolve pharmaceutical processes or tools that aid in increasing efficiency and sustainability. The Analytical Method Greenness Score (AMGS) Calculator and the Process Mass Intensity – Life Cycle Assessment (PMI-LCA) tool will undergo significant improvements to existing functions, and a new biodegradation evaluation process will be developed by the roundtable’s focus teams over the next two years.
Biodegradation Evaluation Process
New legislation in the European Union, such as the EU Green Deal and the EU Urban Wastewater Treatment Directive, have placed the issue of biodegradation into the regulatory landscape, highlighting the need for metrics that can efficiently and accurately rank or predict the biodegradability of molecules. Tobias Harschneck and Tony Reed, ACS GCIPR Biodegradation Focus Team co-leads, describe the need for an efficient and practical biodegradation evaluation process.
“Emerging regulatory frameworks emphasize the need to reduce the environmental impact of active pharmaceutical ingredients (APIs) through design for biodegradability. Currently available methods to assess environmental persistence have long timelines and high costs, rendering them unsuitable for the systematic evaluation of environmental biodegradation of new APIs prior to pre-clinical candidate selection,” says Harschneck.
The Biodegradation Focus Team aims to explore the ability of a medium-throughput assay (using active sludge) from Professor Kathrin Fenner’s lab (EAWAG, Dubendorf, Switzerland) to rank molecules based on their rate of biodegradation and transformation product formation, enabling companies to select pre-clinical candidates that are more consistent with the tenth Principle of Green Chemistry: Design for Degradation. The project’s focus on research-phase APIs makes it unique when compared to other biodegradation assays.
“There are only a few sector-relevant data sources to inform in-silico prediction tools that are specific for APIs. So, while there are some related tools available, the approaches are not fit for purpose. Exploring these new approaches will help to build tools that are specifically relevant for the pharmaceutical industry,” says Harschneck.
The development of an in-silico screening tool would allow biodegradability to be taken into account earlier in the API research and development process, meaning APIs could be designed with biodegradation in mind before they reach the risk assessment stage.
“Systematically investigating the biodegradation of APIs prior to pre-clinical candidate selection would be a fundamental change in drug discovery. It’s exciting to see that we now are entering into the hands-on exploration of new approaches to help make this change to the way research is conducted. This is just the first step, and we remain hopeful that in the future, we will have the ability to design APIs that lack toxicity in both humans and the environment” says Reed.
Analytical Method Greenness Score (AMGS) Calculator
The Analytical Method Greenness Score is an innovative metric developed by the ACS GCIPR to benchmark chromatography method greenness by capturing critical process attributes in order to aid in improving sustainability. Initially published in 2018, the AMGS was developed and tested collaboratively with eight ACS GCIPR member companies with the goal of improving methods and eliminating unnecessary waste from chromatography, a process which traditionally relies on the use of high volumes of solvent.
The web-based, free and publicly accessible AMGS calculator provides metrics for a number of liquid chromatography, mass spectrometry, and supercritical fluid chromatography processes by evaluating sample dissolution, separation method, total solvent use, instruments’ energy consumption, and run time. The resulting greenness score can be used to raise awareness of best practices, promote sustainability in method development, and give a more systemic view of sample handling to increase efficiency. Michael B. Hicks, Associate Principal Scientist at Merck & Co., Inc., Rahway, NJ, USA, and Analytical Chemistry Focus Team co-lead for the ACS GCIPR describes the tool’s impact.
“We believe the AMGS has driven a move towards sustainable methods, a change recognized not only by separation scientists but also by instrument vendors, smaller contractors, and academics. This is reflected in the diverse range of published papers citing the original AMGS paper, which has reached over 170 citations as of May 2025,” says Hicks. “There has been a robust exchange among these teams, fostering continuous improvements in current setups and updates.”
Mary Ellen McNally, FMC Fellow at FMC Corporation, and ACS GCIPR member, who uses the tool, comments, “Here at FMC, we evaluated many of the tools available for establishing a greenness score for an analytical method. The AMGS, analytical method greenness score, was the tool we decided to incorporate into our analytical methods as a sustainable improvement measure. It is simple to use and provides a numerical value that easily shows an improvement as revisions to methods are made.”
Over the next year, the AMGS development team will expand the tool to include gas chromatography, a critical and widely used analytical technique in the pharmaceutical industry. To do this, the tool’s solvent choices will be expanded to cover common solvents analyzed by gas chromatography, and the team will also implement improvements based on feedback from users in both academia and industry.
“We aim to leverage this feedback to eventually encompass all aspects of analytical methods in a future version we call AMGS v2.0. This new version will ideally feature an AI interface and include comprehensive sample preparation steps, from extractions to isolation, lyophilization, and evaporation methodologies,” says Hicks.
Overall, the proposed changes will tailor the tool to the current landscape of the pharmaceutical industry, addressing technological advancements and exigent process concerns. Hicks says, “This new interface will enhance collaboration and leverage modern computational capabilities, making it more relevant for today's needs. Sustainability is not a luxury; it's a necessity in the current industry.”
Process Mass Intensity – Life Cycle Assessment (PMI-LCA) Tool
The PMI-LCA tool is high-level estimator of Process Mass Intensity (PMI) and environmental life cycle information that can be applied to various types of synthesis processes. The tool was launched over a decade ago by the ACS GCIPR, and the most recent version of the tool is available as a downloadable excel file. By combining two important green chemistry metrics—PMI, the ratio of the mass of raw materials to the mass of the final product; and life cycle assessment, a systematic analysis of environmental impact over the course of the entire life cycle of a process— the tool provides a fast and practical assessment of environmental impact of pharmaceutical API manufacturing processes.
As a part of the ACS GCIPR Tools Initiative, the PMI-LCA Focus Team plans to develop a database-enabled online version of the tool to improve ease of use and increase tool adoption. Frank Roschangar, Highly Distinguished Research Fellow – IU Sustainability, Boehringer Ingelheim Pharmaceuticals, Inc., and PMI-LCA Focus Team co-lead, describes what the team hopes to achieve with the panned updates.
“Updating the PMI-LCA tool to a web-based platform will enhance accessibility and usability, supporting standardization of environmental API impact assessments and reinforcing the pharmaceutical industry's leadership in sustainability,” says Roschangar.
The updates represent an important step in the tool’s trajectory, building on its impact on the pharmaceutical industry thus far.
“The PMI-LCA tool has streamlined the estimation of environmental impacts for small molecule API processes, enabling rapid evaluation of process alternatives and promoting greener practices within the industry. I am excited about the tool becoming an industry standard for green manufacturing. The cloud-based tool will facilitate broader adoption and collaboration, significantly enhancing its impact,” says Roschangar.
Isamir Martinez, ACS Green Chemistry Institute Assistant Director and ACS GCI lead for the Roundtable highlights the importance of these three projects for the pharmaceutical industry as a whole.
“To remain on the journey towards sustainability, it is imperative to continue improving and expanding practical and innovative tools and metrics to better design pharmaceutical processes. The ACS GCI Pharmaceutical Roundtable, a unique collaboration between the pharma industry and ACS GCI, has committed to work on this by developing a free, publicly accessible elite tools suite to enable better approaches to chemistry,” says Martinez.
To learn more about the ACS GCIPR and tools from the Roundtable, visit the GCIPR tools page.