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Tools for Innovation in Chemistry

The ACS GCI Pharmaceutical Roundtable is dedicated to the implementation of green chemistry and engineering and member companies have collaboratively developed a variety of high quality tools and metrics to help scientists and engineers make better decisions about chemical selection and route and process design. All tools have been thoroughly vetted by Roundtable companies prior to their public release.

The impetus for tool development can be traced to the late 1990’s when early adopters in the Pharmaceutical industry began asking how green chemistry and engineering could be more broadly implemented in the industry. On the basis of early life cycle inventory/assessment of an active pharmaceutical ingredient, it became clear that chemical selection (i.e., solvents, reagents, etc.) played an enormous role in determining synthetic process cost and environmental, safety and health impacts across the life cycle. This insight led to the development of scientifically valid and industrially relevant bench level tools that could be used by scientists and engineers on a daily basis.

Analytical Method Greenness Score (AMGS) Calculator

Over the last decade, improvements in high pressure liquid chromatography (from HPLC to UHPLC) and supercritical fluid chromatography (from SFC to UHP-SFC) have led to faster and more efficient separations. However, many of these improvements have yet to be implemented. In order to encourage analysts to develop greener methods, the AMGS calculator provides a straightforward metric to enable the comparison of separation methods used in drug development. The AMGS metric includes the solvent health, safety and environmental impact, cumulative energy demand, instrument energy usage, and method solvent waste to benchmark and compare one method to another. The ACS GCI Pharmaceutical Roundtable’s Analytical Chemistry team will be releasing this tool in the late spring 2020.

View the AMGS Calculator

How to Use the AMGS Calculator

Reagent Guides

Reagents are used to effect chemical transformations of all kinds, but generally, there are a limited number of transformations (e.g., oxidations, reductions, eliminations, etc.) that are routinely used by process chemists in developing a synthetic process. However, there are a variety of reagents for any given transformation, and not all reagents have equivalent performance when assessed across a range of green chemistry and engineering metrics. The reagent guides were developed initially within Pfizer to influence medicinal and process chemists to use greener reagents. Based on their success, additional guides were developed by member companies and shared across RT member companies. The reagent guides use Venn diagrams to provide an easy comparison of the scalability, utility, and greenness of reagents. Each reagent is extensively evaluated, examples of use are provided, and a broader greenness assessment with up-to-date references for each reagent is provided. These guides will improve your understanding of greener approaches to chemical transformations and also represent a great resource for educators.

Explore the Reagent Guides

Biocatalysis Guide

The Biocatalysis Guide is a simple double-sided, single-sheet guide to the currently most used enzyme classes amongst the ACS GCI member companies. It has been produced to be an easy to follow guide for chemists who have not had significant exposure to biocatalysis, showing generic transformations that are available so these can be factored into retrosynthetic analysis. In order to keep the sheet easy to read it is not an exhaustive guide to every transformation and it does not carry literature references. The guide can be downloaded and printed for personal use or display in laboratories.

View the Biocatalysis Guide

Solvent Selection Tool

Given the importance of solvents to process mass intensity, solvent selection has been an area of intense interest to Pharma RT member companies. While there are a variety of solvent selection tools available, this is the first tool that has been developed by practicing pharmaceutical process development experts. This interactive tool enables you to select solvents based upon a variety of key solvent properties. Solvents which are close to each other in the principal components (PCA) map have similar properties, whereas distant solvents are significantly different. The tool enables you to download solvent property information such as physical properties, environmental, safety, and health data, etc. Originally developed by AstraZeneca, this tool was recreated for public access by the ACS GCI Pharmaceutical Roundtable.

Access the Solvent Selection Tool

View the Solvent Selection Tool Guide

Green Chemistry Innovation Scorecard Calculator

This tool is a slightly different approach to accounting for PMI by focusing on waste. A joint effort by the IQ Consortium, ACS GCI Pharmaceutical Roundtable, and academic leaders, this Green Chemistry Innovation Scorecard web calculator illustrates how green chemistry and engineering innovation can reduce waste mass during bulk active pharmaceutical manufacture. The calculator uses a statistical analysis of 64 bulk active pharmaceutical manufacturing processes encompassing 703 steps across 12 companies to provide a relative process greenness score. This score may then be used as a means of making meaningful comparisons between different processes and their associated waste reductions.

View the Scorecard Calculator

Read the paper “Inspiring process innovation via an improved green manufacturing metric: iGAL”

View a Presentation about Useful Green Chemistry Metrics

Solvent Selection Guide

Choosing the right solvent is crucial to ensuring a more favorable sustainability profile of a batch chemical manufacturing process common to the pharmaceutical industry. In the pharmaceutical industry, more than 80% of materials used to manufacture bulk active pharmaceutical ingredients are solvents (including water). There are a number of solvent guides in use, including the Roundtable’s simple 2011 guide. However, the most current guide, recommended by the ACS GCI Pharmaceutical Roundtable, is the Chem21 Solvent Selection Guide.

View the Chem21 Solvent Selection Guide

View the Roundtable’s 2011 guide (archived)

MedChem Tips and Tricks

All parts of pharmaceutical development can be made more sustainable. A great example of this is the ACS GCIPR Medicinal Chemistry Team’s approaches to greening medicinal chemistry. The team produced this quick guide covering purification, solvent selection, reagents, energy and resources.

View MedChem Tips and Tricks

Process Mass Intensity (PMI) Metric

Process development chemists and engineers in Pharmaceutical companies are tasked with identifying efficient routes and processes to new chemical entities that become the active pharmaceutical ingredient in final drug products. The efficiency of any molecular synthesis is a combination of the strategy a chemist uses to assemble the different parts of the molecule (i.e., the route to the final target molecule through a series of isolated intermediates) and the subsequent effort to design and optimize the process (i.e., the combination of solvents, reagents, catalysts, process chemicals, etc. that enable bond-making and breaking).

Process mass intensity was proposed as a means of bench marking green chemistry and engineering performance among member companies from the earliest days of Roundtable existence. The first PMI bench marking exercise was held in 2008 and has been held on a regular basis ever since. PMI has helped the industry to focus attention on the main drivers of process inefficiency, cost, and environment, safety and health impact. Consequently, there has been a progression in tool development from a simple PMI calculator to a convergent PMI calculator, to one that allows a streamlined life cycle assessment, to others that allow standardized comparisons and the last which provides estimations of PMI based on the phase of drug development.

The contribution to green chemistry and engineering of this continuing initiative, and the latter two tools in particular, should not be underestimated. The ability to benchmark and predict process mass intensity of processes use to make complex organic molecules will enable scientists and engineers in academia and industry to develop better, more cost effective and more sustainable processes.

Read the OPR&D paper “Using the Right Green Yardstick”

Process Mass Intensity Calculator

Decreasing the overall quantity of materials used to manufacture a final product is a significant challenge for pharmaceutical companies. Because of the large amount of solvent used in typical manufacturing processes, decreasing materials used saves companies money (less purchased and less energy used in workup and isolation). The Process Mass Intensity (PMI) metric was developed as a way to benchmark and quantify improvements towards greener manufacturing processes. The PMI Calculator enables you to quickly determine the PMI value by accounting for the raw material inputs on the basis of the bulk API output.

Download the Process Mass Intensity Calculator

View the Presentation: Pharma and Suppliers: Collaborating on Green Chemistry; Launch of PMI Tool.

Convergent Process Mass Intensity Calculator

The original PMI calculator was enhanced to accommodate convergent synthesis in this second ACS GCI Pharmaceutical Roundtable PMI calculator. The Convergent PMI Calculator uses the same calculations, but allows multiple branches for single step or convergent synthesis.

Download the Convergent Process Mass Intensity Calculator

View the Presentation: ACS GCI Pharmaceutical Roundtable’s Convergent PMI Calculator

NEW: Process Mass Intensity Life Cycle Assessment

The PMI-LCA Tool is a high-level estimator of Process Mass Intensity (PMI) and environmental life cycle information that can be customized to fit a wide variety of linear and convergent processes for synthesis of small molecule active pharmaceutical ingredients (APIs). An ecoinvent dataset is utilized as the source of the life cycle impact assessment (LCIA) data.

Download the PMI-LCA Tool

PMI-LCA Tool Quick-Start Guide

Process Mass Intensity Prediction Calculator

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.

View the PMI Prediction Calculator

Read the paper “The PMI Predictor – a Web App Enabling Green-by-Design Chemical Synthesis”

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