After the announcement a few years ago of new toxicological data for Isopropylbenzene (Cumene), there was a need to assign this solvent to the higher Class 2 (previously Class 3 - solvent with low toxicity). As a consequence, the ICH Guideline Q3C(R4) had to be revised, for the fifth time. The ICH Draft Consensus Guideline called "Impurities: Guideline for Residual Solvents - PDE for Cumene" published on 26 March for comment (see our News from 1. September 2010 ) has been integrated into the core document Q3C(R4) and the tables on the solvents' classes have been accordingly updated.
The final Guideline Q3C(R5) is dated 4 February 2011 and was published on the ICH Website on 16 February.
For API and medicinal products manufacturers who use Cumene as a solvent in their processes, the assignment to a more toxic solvent class means that the authorisation documents may have to be reviewed on certain points since the maximum amount of this solvent incorporated with a medicinal product (PDE = permitted daily exposure) must now be calculated differently.
You can find the new Guideline Q3C(R5) here.
Note: the residual solvents topic und the calculation of their limits will be discussed during the ECA course „Impurities" which will take place on 25-27 May 2011 in Budapest, Hungary.
Dr Gerhard Becker
CONCEPT HEIDELBERG (a service provider entrusted by the ECA Foundation)