Nudelman ChemTox
Consulting
Mutagenic Impurities
This service surrounds assessment and qualification of potential mutagenic impurities according to the ICH M7 guidelines.
This service includes:
Computational assessments (in silico) for potential mutagenic impurities
The assessment uses advanced computational tools and models to predict whether a chemical compound or impurity has mutagenic potential. QSAR (Quantitative Structure-Activity Relationships) tools such as Lhasa’s Derek Nexus and Sarah Nexus, MultiCase’s Case Ultra and Instem’s Leadscope are used to identify structural alerts and predict mutagenicity based on chemical structure.
Read-across techniques
Read across is a method suggested by the ICH M7 guideline in order to assess potential mutagenic impurities that lack experimental data based on comparison to surrogate compounds that have similar structural alerting features, and that have sufficient experimental data to set acceptable intake limits.
Control limit recommendations
Control limits are essential for ensuring product safety and regulatory compliance. This service focuses on:
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Control limit recommendations allow manufacturers to set actionable and safe thresholds for monitoring impurities during production and quality control.
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Ensuring compliance with international guidelines, such as those outlined by ICH Q3A/B, M7, and S9 while addressing industry-specific needs.
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Establishing scientifically justified thresholds for specific impurities, particularly those with mutagenic or carcinogenic concerns, using the in silico predictions described above, read-across, and other techniques.
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Modifications and adjustments to default TTC (Threshold of Toxicological Concern) limits.
Ames test coordination:
The Ames test is a gold standard in vitro reverse mutation bacterial assay for evaluating the mutagenicity of substances. This service supports clients by:
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Identifying suitable contract research organizations (CROs) or testing laboratories.
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Coordinating the test design, including strain selection, concentrations, and controls.
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Ensuring adherence to GLP (Good Laboratory Practices) and relevant standards.
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Interpreting the test results and integrating them into broader risk assessments or regulatory submissions.
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This service bridges the gap between in silico predictions and experimental validation, ensuring comprehensive toxicological evaluations.