Investigational

Setting limits based on toxicity data?
NOVARTIS
Toxic residual solvents/heavy metal catalysts limits are described in ICH
or CPMP guidances (or draft guidance)
However, there are extensive discussions in the quality and safety
community on what are suitable/acceptable limits e.g. for genotoxins
‣ Few compounds are sufficiently experimentally characterized (e.g. in rodent
carcinogenicity studies) to do a reliable risk assessment
‣ The draft position paper from the CPMP Safety Working Party is not very
clear on this issue
‣ Extensive comments via EFPIA and PhRMA have been submitted
‣ It appears that the EFPIA proposal to adopt the concept of a “Threshold of
Toxicological Concern (TTC) as applied in the food contact substances area
may be acceptable to the CPMP
‣ TTC lies at 1.5ug/day for lifetime exposure
(exceptions: very potent carcinogens such as a few nitrosamines)
‣ Proposed ICH topic?
L. Müller, Swissmedic, 21-Oct-2003