Page 4 - Shimadzu’s Solutions for Impurities Analysis

Support for FDA Regulations on Residual
Solvents in Pharmaceuticals

The ICH guideline, "Impurities: Guideline for Residual In 2008 the FDA issued a draft guidance, "Residual Solvents
Solvents" (ICH Q3C), has recommended the use of in Drug Products Marketed in the United States," that
low-toxicity solvents for the manufacture of required support, analysis, and testing according to the
pharmaceuticals and indicated toxicity threshold values for new USP <467> Residual Solvents method.
several solvents. The ICH guidelines did not define detailed analysis
Residual solvents in pharmaceuticals are defined as volatile procedures but stated that "Residual solvents are typically
organic compounds used or generated at the determined using chromatographic techniques such as gas
manufacturing stage of pharmaceuticals, pharmaceutical chromatography. Any harmonised procedures for
ingredients or additives. They are divided into three classes determining levels of residual solvents as described in the
according to a risk assessment. pharmacopoeias should be used, if feasible. Otherwise,
manufacturers would be free to select the most appropriate
• Class 1 solvents: Solvents to be avoided validated analytical procedure for a particular application."
Known human carcinogens, strongly suspected human However, the new USP <467> Residual Solvents method
carcinogens, and environmental hazards. prescribes GC headspace analysis based on the European
Pharmacopoeia (EP).
• Class 2 solvents: Solvents to be limited The new USP <467> Residual Solvents method recognizes
Non-genotoxic animal carcinogens or possible causative an integration calculation method based on test results on
agents of other irreversible toxicity such as neurotoxicity the ingredients and excipients instead of residual solvent
or teratogenicity. Solvents suspected of other significant testing on the final pharmaceuticals. If this standard is
ɹbut reversible toxicities. satisfied, it is not necessary to test for residual solvents in
the final pharmaceutical product.
• Class 3 solvents: Solvents with low toxic potential
Solvents with low toxic potential to man.