At the beginning of this year, the European Medicines Agency (EMEA) published a question-and-answers document on the limits for genotoxic impurities. It is the objective of this Q-and-A document to answer frequently asked questions regarding the Guideline on the Limits of Genotoxic Impurities (EMEA/CHMP/QWP/251344/2006).

Question 1 reads:

The guideline does not need to be applied retrospectively to authorised products unless there is a specific cause for concern. What might constitute "a cause-for-concern" in terms of application to currently marketed products?

Answer:
If a manufacturing procedure for API remains essentially unchanged a re-evaluation with respect to the presence of potentially genotoxic impurities is generally not needed. However, new knowledge may indicate a previously unknown cause for concern. One example is the mesylate salt drug substances for which a few years ago, a concern regarding the potential for formation of genotoxic alkyl mesylates was raised. This concern resulted in the "Production Statement" requesting a specific evaluation of the potential for formation of these highly toxic products now included as part of the PhEur monographs for all the mesylates salts.

Get more information on impurities and on the guideline on genotoxic impurities at the ECA Conference: Impurities from 27–28 May in Prague, Czech Republic.

EMEA's complete Q-and-A document can be found here:
http://www.emea.europa.eu/pdfs/human/swp/43199407en.pdf


Compiled by:
Oliver Schmidt
On behalf of the European Compliance Academy (ECA)