N-Nitrosamines (NAs) are probable human carcinogens and are part of the cohort of concern in the ICH M7(R2) guidance on impurities in pharmaceuticals. To address the lack of standard experimental design for detecting NA-induced genotoxicity in mammalian cells, Toxys developed the Enhanced Metabolization Protocol (EMP). This protocol greatly improves bioactivation of NAs and increases the sensitivity of ToxTracker, a mammalian cell-based GFP reporter assay, to detect the harmful effects of these NAs.

Due to the large number of Nitrosamine Drug Substance Related Impurities (NDSRIs) that have been reported in recent years, read-across is encouraged in regulatory guidance in lieu of experimental data. Read-across typically requires the assessment of similarity across many dimensions, from structural features to physicochemical properties. From these, Lhasa Limited defines the mechanism of action and provide an estimate of how comparable the potencies of the query and potential analogue are. Finally, we can assess the quality of available toxicological data to derive a suitable intake limit. These steps can be organized into a systematic workflow, which has been developed to support read-across assessments. This process, if manual, is time consuming and requires a lot of expertise, but has been automated in a harmonized in silico solution by Lhasa Limited with confidence measure to support your decision. If the data is carcinogenicity data, this is an acceptable intake from a TD50; however, other types of toxicity data require the calculation of benchmark doses (BMDs) and subsequently a permitted daily exposure (PDE). These can be used to benchmark a variety of types of toxicity data against the potency of relevant surrogates – the challenge in this exercise is determining which compounds to use as benchmarks.

Join Toxys and Lhasa Limited in this webinar in which we will introduce the EMP and its qualification and discuss effective evaluation of N-nitrosamine driven genotoxicity in mammalian cells.

During this webinar, you will learn:

• Enhanced Metabolization Protocol and its qualification
• Evaluating the genotoxic potential of N-nitrosamines with ToxTracker EMP
• Strategies for determining safe intake limits for nitrosamines by read-across

Presentations:

Introduction to Toxys service portfolio

Elias Halkes-Wellstead, Director BD & Sales at Toxys
Host

Enhanced Metabolization Protocol (EMP) for the ToxTracker assay

Dr. Inger Brandsma, Director Genetic Toxicology at Toxys
Presenter

Strategies for determining safe intake limits for nitrosamines by read-across

Dr. David Ponting, Senior Principal Scientist at Lhasa Limited
Presenter

Webinar on ToxTracker EMP

When: 28 October 2025, 4:00-5:00 pm CET