Regulatory starting materials (RSMs) represent the starting point of drug substance synthesis from which subsequent steps are carried out under good manufacturing practice (GMP) and the point from which regulatory oversight largely begins. Drug substances are then formulated with excipients to manufacture drug products. With regard to small molecules, RSMs are simpler chemical structures that are introduced a number of synthesis steps prior to the final drug substance and that represent a significant structural fragment (i.e., they are not a reagent or other raw material). RSMs are a critical quality component of a medicinal product, as they can impact the impurity profile of the drug substance and consequently the drug product. Given their criticality to the quality and safety of a medicinal product, deficiency points on RSMs are typically raised as major objections during the new drug application (NDA) and marketing authorization application (MAA) reviews…
