Development of a Manufacturing Process for S-892216 Part II: Improvements Toward Commercially Feasible Process

In this study, we described developing a refined manufacturing process for S-892216, a second-generation COVID-19 therapeutic agent currently under development. The focus of this research was on the feasibility of commercial manufacturing. In particular, we developed a manufacturing process that facilitates the stable acquisition of a specific crystal form for intermediate or maximum reaction efficiency using flow chemistry, eliminating the need for excessive extraction, concentration, and purification operations. Compared to the first-generation process used during early-phase clinical trials, the overall yields (increasing from 41% to 62%) and PMI values (decreasing from 323 to 210) improved significantly. These advancements underscore the potential of the second-generation process for S-892216 to strengthen the supply chain of COVID-19 therapeutics.