ICH Issues New Guidance on Two Pharmaceutical Solvents

August 4, 2015

The International Conference on Harmonisation is recommending that drugmakers limit their use of the solvent methylisobutylketone in drug products after two studies showed toxicity in rats and mice.

Based on that data, ICH has classified it as a group 2B carcinogen, meaning it is possibly carcinogenic to humans.

The decision — outlined in revised guidance on permitted daily exposure to MIBK and triethylamine — calls for MIBK to be moved from Class 3 (low-toxicity potential) to Class 2 (solvents with inherent toxicity). ICH’s Expert Working Group released the guideline on Wednesday.

In MIBK’s place as a new Class 3 solvent, ICH is proposing the catalytic solvent triethylamine. In tests, TEA showed no reproductive toxicity, genotoxicity or repeated dose toxicity. No carcinogenicity data was available, but ICH is recommending it be labeled as a solvent with low toxic potential and, therefore, usable in manufacturing drugs.

Drugmakers may submit comments until Dec. 31 by emailing the ICH secretariat at step2comments@ich.org. View the draft Q3C (R6) guideline at www.fdanews.com/07-30-15-ICHQ3CR6.pdf . — Kellen Owings