Under ICH M7, impurities are assessed using the bacterial reverse mutation assay (ie, Ames
test) when predicted positive using in silico methodologies followed by expert review. N-…

Low levels of N-nitrosamines (NAs) were detected in pharmaceuticals and, as a result,
health authorities (HAs) have published acceptable intakes (AIs) in pharmaceuticals to limit …

Enhanced sensitivity of analytical chemistry methods has enabled the detection of low-levels
of pharmaceuticals in the environment, resulting in questions about the safety of surface …

N-Nitrosodiethylamine (NDEA), a well-studied N-nitrosamine, was tested in rats to compare
the dose-response relationship of three genotoxicity endpoints. Mutant / mutation …

Quantitative methods for estimation of cancer risk have been developed for daily, lifetime
human exposures. There are a variety of studies or methodologies available to address less-…

The Acceptable Daily Exposure (ADE) derived for pharmaceutical manufacturing is a health-based
limit used to ensure that medicines produced in multi-product facilities are safe and …

The ICH M7(R1) guideline describes a framework to assess the carcinogenic risk of mutagenic
and carcinogenic pharmaceutical impurities following less-than-lifetime (LTL) exposures. …

This manuscript discusses the different historical and more recent default approaches that
have been used to derive an acceptable daily exposure (ADE). While it is preferable to derive …

This symposium focuses on the management of genotoxic impurities in the synthesis of
pharmaceuticals. Recent developments in both Europe and United States require sponsors of …

In order to determine a threshold for nongenotoxic carcinogens, the traditional risk
assessment approach has been to identify a mode of action (MOA) with a nonlinear dose–response. …