Chapter 7 - Residual solvents

Abstract

Residual solvents comprise one of the classes of potential impurities in drug products. For most residual solvents, sufficient toxicological data exist to allow solvents to be classified according to their toxicological potential. The most toxic solvents (Class 1) are to be avoided, and the use of the least toxic solvents (Class 3) is encouraged. The safe permitted daily exposure to a particular solvent has been calculated for most of the solvents in use in pharmaceutical production, and those exposure limits provide the basis for establishing acceptance criteria for the residual solvents in pharmaceutical products. Drug products may be tested directly, or the components of the drug product may be tested individually. Detailed pharmacopeial test methods are available, but manufacturers are free to implement their own validated methods. Various testing strategies are reviewed, and testing requirements according to the class of the solvent are described. Validation of methods should be conducted in accordance with the principles discussed in ICH guideline Q2.