Toxway offers detailed Genotoxicity and Mutagenicity Assessments for drug impurities, ensuring compliance with the stringent requirements of ICH M7 guidelines. These evaluations are essential for identifying and controlling impurities that may pose genotoxic or mutagenic risks, which are critical in drug development and manufacturing processes. Our precise assessments provide the necessary data to support your regulatory submissions, helping to safeguard patient safety and maintain product integrity.
Our Genotoxicity/Mutagenicity Assessment Services Include:
Identification of Potentially Genotoxic Impurities (PGIs):
We identify and evaluate impurities in drug substances and drug products that have the potential to be genotoxic (damage genetic material) or mutagenic (cause mutations). These impurities can arise during manufacturing processes, degradation, or as by-products of chemical reactions. Our focus is to detect impurities early, enabling timely risk management.
Structure-Activity Relationship (SAR) Analysis:
One of the key methods we use for genotoxicity assessment is SAR analysis, where we assess the chemical structure of impurities to predict their genotoxic potential. By comparing the impurity’s molecular structure with known genotoxic compounds, we determine the likelihood of genotoxicity based on structural alerts.
In Silico (Computational) Models for Genotoxicity Prediction:
We apply advanced in silico models such as QSAR (Quantitative Structure-Activity Relationship) and Derek Nexus to predict the genotoxic potential of drug impurities. These tools provide rapid, reliable predictions without the need for laboratory testing, saving time and resources while meeting ICH M7 requirements.
In Vitro and In Vivo Testing Recommendations:
When structural alerts are identified or further investigation is needed, we provide recommendations for targeted in vitro and in vivo tests. Common tests include:
Ames Test: To assess mutagenic potential in bacterial cells.
Chromosomal Aberration Test: To detect chromosomal damage in mammalian cells.
Micronucleus Test: To evaluate genotoxic effects on bone marrow or peripheral blood cells in vivo.
Threshold of Toxicological Concern (TTC) Approach:
For low-level impurities, we apply the TTC (Threshold of Toxicological Concern) approach to determine whether the impurity level poses a significant genotoxic risk. This approach sets acceptable exposure limits for impurities with minimal available toxicological data, reducing unnecessary testing while ensuring safety.
Quantitative Risk Assessment (QRA):
In cases where impurities are shown to have genotoxic potential, we conduct a Quantitative Risk Assessment (QRA) to establish safe exposure limits based on available data. This involves calculating acceptable intake levels to ensure that the impurity does not pose an unacceptable risk to patients over the course of treatment.
Assessment of Degradation Products:
We evaluate the genotoxic potential of degradation products that can form during drug manufacturing, storage, or transport. Degradation products can introduce new genotoxic risks, making it crucial to assess their impact on the drug’s safety profile.
Regulatory Compliance with ICH M7:
Our genotoxicity/mutagenicity assessments are fully aligned with ICH M7 guidelines, which emphasize the identification and control of genotoxic impurities. We ensure that all potential mutagenic or genotoxic risks are thoroughly assessed and mitigated before your drug product reaches the market.
Safety Margin Calculation and Risk Control:
We calculate the safety margins for genotoxic impurities and propose appropriate control strategies to minimize patient exposure. This includes recommendations for adjusting manufacturing processes, impurity specifications, or introducing analytical methods for impurity detection and control.
Documentation for Regulatory Submission:
We provide clear, detailed reports that summarize our findings, including the results of SAR analyses, in silico predictions, and any relevant in vitro or in vivo tests. Our reports are designed to meet regulatory expectations and support your submission to agencies like FDA, EMA, MHRA, and other global health authorities.
Integrated Risk Management Strategies:
Based on our assessments, we offer tailored risk management strategies to control genotoxic impurities throughout the drug development and manufacturing process. This can include adjustments to synthetic routes, impurity specifications, or enhanced purification steps to mitigate risks.
Why Genotoxicity/Mutagenicity Assessment Matters: Controlling genotoxic and mutagenic impurities is a critical aspect of ensuring drug safety. At ToxWay, our thorough evaluations based on ICH M7 guidelines provide you with the insights needed to identify, assess, and mitigate the risks associated with these impurities. By leveraging advanced computational tools, in-depth SAR analysis, and targeted testing, we help you meet regulatory requirements and protect patient safety, ultimately streamlining your product’s path to market.
For more information about our services or to request a consultation, contact us at info@toxway.com
