Investigational

General approach for identification and
qualification of impurities
NOVARTIS
Impurities are normally qualified in appropriate toxicological studies as part
of a drug substance or drug product
‣ It is assumed that their structure is normally close to that of the drug substance
The toxicological qualification threshold for drug substance impurities is
0.15% (0.5% for daily dose of more than 2g) = 1500ppm (or 500ppm)
The (structure) identification threshold is 0.1% (or 1mg/day,
whichever is lower)
‣ (0.5% for daily dose of more than 2g) = 1000ppm (or 500ppm)
Essential qualification studies are
‣ Genotoxicity in vitro
‣ A (sub) chronic toxicity study (in rodents)
Specifications/levels in clinical batches should be covered by tox
investigations
‣ Either in acutal percentage
or
‣ with appropriate safety factors
L. Müller, Swissmedic, 21-Oct-2003