Safe Scale-Up of Pharmaceutical Manufacturing Processes with Dimethyl Sulfoxide as the Solvent and a Reactant or a Byproduct

Thermal hazard analyses of two reactions, one with DMSO as the solvent and a reactant and one with DMSO as the solvent and a byproduct, identified low-probability but severe consequence process risks associated with violent decomposition of DMSO during heating control failure or external heating. Although DMSO cannot be totally eliminated from these reactions, using an alternative solvent to replace DMSO proved to be an effective measure in reducing the thermal hazards to allow safe scale-up.