Residual Solvents

Residual Solvents

Note for Guidance on Impurities: Residual Solvents

The European Agency for the Evaluation of Medicinal Products Human Medicines Evaluation Unit

CPMP/ICH/283/95, March 1998, ICH Harmonised Tripartite Guideline Q3C

The limits for residual solvents given in Ph Eur, USP and JP are based on the Guidelines for Residual Solvents (CPMP/ICH/283/95, March 1998) which were adopted by the International Conference on Harmonization (ICH) for registration of pharmaceuticals for human use and prescribe limits for the content of solvents which may retain in active substances, excipients and medicinal products after processing. The residual solvents are listed in Appendix 1 by common names and structures. They were evaluated for their possible risk to human health and placed into one of three classes as follows:

Class 1 solvents: Known human carcinogens, strongly suspected human carcinogens, and environmental hazards. They are listed in Table 1.

Class 2 solvents (solvents to be limited): Non-genotoxic animal carcinogens or possible causative agents of other irreversible toxicity such as neurotoxicity or teratogenicity. They are listed in Table 2.

Class 3 solvents (solvents with low toxic potential): Solvents with low toxic potential to man; no health-based exposure limit is needed. Class 3 solvents have PDEs of 50mg or more per day. They are listed in (Definition of PDE: Permitted daily exposure).

Further information: www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002674.pdf and www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_000431.jsp&jsenabled=true