A cheminformatics-based methodology to incorporate safety considerations during accelerated process development

Abstract

The fine chemical industry regularly develops novel products for diverse applications and produces them at scale in multi-purpose, batch processes. These processes often involve highly hazardous chemicals and reactive chemical hazards. If an unacceptable risk is identified after the production route has been finalized, it would necessitate expensive redesigns and result in suboptimal risk management strategies with significant delays in time to market. It is, therefore, desirable to consider inherent safety analysis during route selection. The traditional methods for inherent safety analysis are not directly applicable to the fine chemicals industry which have unique characteristics; specifically, they require information on a large number of properties of materials and reactions, which are not usually available for novel pathways, especially at the route selection stage. While safety data could be determined experimentally, this would be time-consuming and expensive, especially if the route were to be rejected later in the process development. In this paper, we propose a practicable methodology that addresses these important challenges unique to fine chemicals industry. Our methodology leverages chemoinformatic models, which are increasingly becoming available and reliable, to estimate material and reaction properties. Various chemoinformatic models are systematically integrated into the process development workflow so that fire, toxicity, and reactivity hazards can be estimated when necessary, thus enabling inherently safer route selection. The methodology is illustrated using an industrial case study of Boscalid manufacture. Fifty-three safety-critical properties are predicted using various chemoinformatics methods and enable the identification of safety issues at the early stages of the process lifecycle.