This team is designing an interactive acid-/base tool combining physical properties and SHE data.

This team explores computer-assisted approaches and tools to prioritize and guide experiments and deliver green chemistry outcomes. Artificial Intelligence (AI), or Machine Learning, has many potential applications within green chemistry.

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. The team recently developed a new 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.

Green chemistry programs can have a measurable impact on the reduction of raw materials consumed to manufacture an API, as well a decrease in the quantity and potential toxicity of waste. As a result, green chemistry metrics should contribute to larger corporate sustainability goals. However, better communication and reporting may help connect green chemistry programs to broader, and more publicly visible, goals such as carbon footprinting, greenhouse gas reduction, water use reduction, etc. This team gathers and shares best practices to link green chemistry to corporate sustainability commitments.

This team publishes biannual reviews of recent literature of interest realted to the Roundtable’s Key Research Areas. Current topics include amide formation, C-H activation, fluorination green solvent replacements and activation of alcohols for nucleophilic displacement.

The Award Team is organized to recognize excellence in the research, development and execution of green chemistry that demonstrates compelling environmental, safety and efficiency improvements over current technologies in the pharmaceutical industry and its allied industrial partners.

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.

Biologics are a growing sector of the pharmaceutical industry and have become a significant portion of many companies’ pipelines. The BioPharma focus group seeks to improve the environmental footprint of biologics development and manufacture through the adaptation and implementation of green chemistry and engineering principles.

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.

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.

The ACS GCI Pharmaceutical Roundtable puts a priority on educating and influencing current and future pharmaceutical leaders on the business and scientific value of green chemistry and engineering within the industry. The goal of the Educating Leaders Team is to educate scientific and business leaders in addition to potential Roundtable members.

Integrating green chemistry and engineering into the global pharmaceutical supply chain is a primary objective of the Global Collaborations Team. The Roundtable dedicates resources to international workshops, conferences and site visits and has member companies based across the US, Europe, and Asia.

The ACS GCI Pharmaceutical Roundtable has identified key synthetic chemistry and process research challenges whose solutions would result in more efficient pharmaceutical process development and production. To spur research in these areas, the Roundtable created and maintains a research grant program, whose impact over the years has been recently documented. The Roundtable also advocates for targeted green chemistry and engineering support to academic and government labs from international and U.S. federal funding agencies.

Green chemistry programs can have a measurable impact on the reduction of raw materials consumed to manufacture an API, as well a decrease the quantity and potential toxicity of waste. As a result, green chemistry metrics should contribute towards larger corporate sustainability goals. However, better communication and reporting may help connect green chemistry programs to broader, and more publicly visible, goals such as carbon footprinting, greenhouse gas reduction, water use reduction, etc. This team will gather and share best practicies to link green chemistry to corporate sustainability commitments.

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. 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. The team is organizing around benchmarking, best practice sharing, and the identification of new synthetic methodologies in an attempt to reduce the environmental impacts associated with these processes.

This 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. The synthesis of peptides and oligonucleotides is associated with the use of comparatively high volumes of solvent. Roundtable member companies have organized around benchmarking, best practice sharing, and the identification of new synthetic methodologies in an attempt to reduce the impacts associated with these processes.

This team explores ways to improve commercial processes on cost factor by using techniques such as Lean to allow material resource intensity to be considered during manufacturing.

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. The Medicinal Chemistry sub-team is organized for best practice sharing and have identified a variety of useful practices to green medicinal chemistry.

The Process Mass Intensity (PMI) Prediction Calculator was created by the ACS GCI Pharmaceutical Roundtable member companies, with leadership from Bristol-Myers Squibb, to predict a range of probable process efficiencies of proposed synthetic routes at various phases of drug development. The tool uses historical PMI data from multiple pharmaceutical companies and predictive analytics (Monte Carlo simulations) to estimate the probable PMI ranges. The tool can be used to predict PMI prior to any laboratory evaluation of the route; i.e., as an in-silico modeling effort, or at any other stage of a molecule’s development to assess and compare potential route changes.

This excel tool is intended as a high-level estimator of process mass intensity (PMI) and environmental life cycle assessment (LCA) that can be customized to fit a wide variety of linear and convergent processes for small molecule APIs. The streamlined tool is not comprehensive but “fit for purpose” to benchmark and quantify improvements towards greener and more sustainable manufacturing processes by displaying trends in environmental footprint reduction.

The REACH sub-team ensures the strong connection between chemical legislation and green chemistry is recognized, understood and communicated transparently within our member companies. Chemical legislation usually impacts where there is concern for potential harm to human health or environmental detriment. REACH (Registration, Evaluation, Authorization and Restriction of Chemicals) is the most notable and arguably the most proactive of the variety of chemical legislation that exists. For this reason, it is the team’s focal point (but not the alone) in the groups review and consideration of business impact.

There are seven new guides planned for deployment in 2019 including key pharmaceutically-relevant transformations such as amide bond formation, fluorination and biocatalysis. Development of the new guides is carried out by team members in partnership with Andy Wells (Charnwood Consulting).The team have actively embedded a feedback loop within the guides in order for suggestions to be made regarding references on new reports to be considered for inclusion in a current guide as well as potential proposals for new transformations to be covered in future guides.

The Roundtable has developed and endorsed a number of solvent guides over the years to address the important issue of solvents which account for more than 80% of materials used to manufacture bulk pharmaceutical ingredients. The current guide recommended by the Roundtable is the Chem21 Solvent Selection Guide which will provide an assessment of a solvent. In addition, AstraZeneca developed an interactive Solvent Selection Tool in Spotfire allowing process needs and environmental perspectives to be evaluated in a single exercise.

The supply chain focus team works to identify and address synthesis issues of purchased raw materials.