FDA Implements ICH Guidelines for Three Solvents

In a final guidance released Dec. 10, the FDA adopted International Council for Harmonization (ICH) guidelines for three solvents used in drug manufacturing processes, based on the most up-to-date data on reproductive, genetic and carcinogenic toxicities.

In the 13-page guidance, titled Q3C(R8) Impurities: Guidance for Residual Solvents, the agency recommended permitted daily exposures (PDEs) for 2-methyltetrahydrofuran(2-MTHF), cyclopentyl methyl ether (CPME) and tertiary-butyl alcohol (TBA).

2-MTHF, which is a solvent with low toxic potential, has a recommended PDE of 50 mg per day, the agency said. CPME, which is used in pharmaceutical chemical development as an alternative to tetrahydrofuran and tert-butyl methyl ether, has a recommended PDE of 15 mg per day. Because of its carcinogenic potential, it should be placed into class 2 “Solvents to Be Limited,” the agency said.

TBA, which has many uses, including as a denaturing agent and solvent, should be placed into class 2 with a PDE of 35 mg per day, the agency said.