PHARMACOPOEIAL APPROACHES TO RATIONING RESIDUAL ORGANIC SOLVENTS IN MEDICINES

The presence of residual organic solvents (toxic impurities) may be hazardous to patients. Therefore, pharmacopoeias include articles (monographs) governing their definition and rationing. The contents of general pharmacopoeia articles of the State Pharmacopoeias of the Russian Federation, XII and XIII editions, monographs of the European Pharmacopoeia, and the U.S. Pharmacopoeia, their structures, and terminologies were comparatively analyzed. Two different approaches to rationing residual organic solvents in the active pharmaceutical substance, excipients, and medicines are noted. The paper shows a need for the further harmonization of Russian normative documents (NDs) for the impurities of residual organic solvents. It indicates that the draft NDs should include additional sections on methods for establishing a partial differential equation (PDE), by describing the principle in the determination of toxicity for each of the hazard classes, the formulas to calculate the PDE and all modifying factors. Emphasis is placed on the importance of complementing the draft with conceptual information sections.