The Evolution of High-Throughput Experimentation in Pharmaceutical Development and Perspectives on the Future

TLDR

High‑throughput experimentation has transformed pharmaceutical development by enabling rapid screening of compound libraries and, over the past decade, extending its principles to small‑molecule process chemistry, prompting major companies to establish dedicated HTE groups and invest in automation that accelerate process development. This review provides an overview of current best practices in process chemistry, discusses frequently studied transformations, offers a perspective on the field’s future, and outlines manual and automated tools to facilitate experimentation. Case studies illustrate state‑of‑the‑art workflows developed in the authors’ laboratories.

Abstract

High-throughput experimentation (HTE) has revolutionized the pharmaceutical industry, most notably allowing for rapid screening of compound libraries against therapeutic targets. The past decade has also witnessed the extension of HTE principles toward the realm of small-molecule process chemistry. Today, most major pharmaceutical companies have created dedicated HTE groups within their process development teams, invested in automation technology to accelerate screening, or both. The industry's commitment to accelerating process development has led to rapid innovations in the HTE space. This review will deliver an overview of the latest best practices currently taking place within our teams in process chemistry by sharing frequently studied transformations, our perspective for the next several years in the field, and manual and automated tools to enable experimentation. A series of case studies are presented to exemplify state-of-the-art workflows developed within our laboratories.