(423e) PRIME: Process Ranking of Inputs from Manufacturing and Environment

This work presents a newly developed knowledge-based assessment tool intended to evaluate and classify API synthesis processes, this way guiding drug development in providing reliable and efficient processes at a rapid pace. This tool incorporates commonly known green chemistry metrics, including atom economy, E-factor, volume-time-output, and the semi-quantitative EcoScale tool.[1], [2] Additionally the recent concept developed by the IQ consortium of the innovation green aspiration level (iGAL) is also being calculated in the tool.[3]

The concept of green chemistry proposed to change the way chemistry and chemical engineering was done, by enabling a "greener" and sustainable process, which involved waste prevention, lower energy consumption, synthetic efficiency, and reduced hazardous components (used and generated). To reduce the subjectivity inherent in this type of evaluation, scientists have developed several quantification metrics over the years, which would allow for a clear and fast way to obtain information on the greenness of any type of chemical process, resorting to simple mass and energy calculations, health, safety and environmental (HSE) considerations, and lifecycle impact approaches. These metrics would also enable to predict how a certain modification, such as replacement of a solvent or elimination of a unit operation, would influence the environmental impact and efficiency of a process.

However, these metrics often represented individual approaches of evaluating one single aspect of the API process, this way not providing enough information to fully evaluate its efficiency, for it depends on numerous factors. Therefore, only a holistic approach of assembling several relevant green metrics can provide an adequate assessment of chemical processes.

By gathering all these inputs and assembling them in a structured framework, chemical processes can be evaluated in terms of synthesis strategy, waste generation, productivity, quality, process conditions, raw materials classification, and health, safety and environmental considerations, achieving a final classification based on every single one of these key aspects to truly determine process efficiency. The developed assessment tool was successfully implemented on various drug development projects, providing cross-project comparison and the creation of a centralized database for the company's process knowledge. Additionally, a critical aspects analysis allowed for a rapid detection of what criteria should be improved on a given process, and a case study evaluation of a project with multiple process revisions over time allowed for its improvement-evolution assessment.

References:

[1] R. Dach, J. J. Song, F. Roschangar, W. Samstag, and C. H. Senanayake, “The Eight Criteria Defining a Good Chemical Manufacturing Process,” Org. Process Res. Dev., vol. 16, no. 11, pp. 1697–1706, Nov. 2012.

[2] D. J. C. Constable, A. D. Curzons, and V. L. Cunningham, “Metrics to ‘green’ chemistry - Which are the best?,” Green Chem., vol. 4, no. 6, pp. 521–527, 2002.

[3] F. Roschangar et al., “Inspiring process innovation via an improved green manufacturing metric: iGAL,” Green Chem., vol. 20, no. 10, pp. 2206–2211, 2018.