Genetic toxicology services for ICH S2(R1) compliance
Genotoxicity
Assessment of genotoxicity is critical for prediction of mutagenicity and later carcinogenicity. Genotoxicity potential of an active ingredient can be an important indicator for mutagenic and thus carcinogenic effects of any drugs. Genotoxicity of impurities must also be controlled. To obtain information on genotoxicity of a compound, several combined tests are required in different test systems and need the assessment of multiple endpoints. Based on the interpretation of results , a final safety assessment for the substance can then be done in line with all Health Agencies’ guidelines (eg US Food and Drug Administration (US FDA), European Medicine Agency (EMA), Pharmaceutical and Medical Device Agency (PMDA) and in compliance with the International Council for Harmonization (ICH) regulation).
Complete Genotoxicity Testing – All from One Source
For screening purposes, working with us will allow you to get a clearer idea on the genotoxicology profiles of your drug candidates, during the lead selection phase. With the support of our expert team, you can also accelerate your discovery pipeline through a tailored screening strategy that combines in silico (QSAR) and in vitro approaches (mini-Ames, micronucleus).
For regulatory purposes, we can design and execute a complete set of regulatory-compliant tests in our GLP-certified laboratories aligned to the best regulatory options, based on your drug class and therapeutic areas, by using in vitro and in vivo tests.
Discuss your genotoxicity testing needs with us:
ICH S2(R1) Test Batteries for Regulatory Genotoxicity Assessment
According to ICH S2(R1), two alternative test batteries may be applied to assess the genotoxic potential of drugs.
Assessment of Mutagenic Properties of Impurities
All drug products may contain some impurities related to the choice of synthetic routes for producing them. Those impurities may also arise during the manufacturing processes from interaction between the drug active substance and excipients, or packaging materials, or by degradation of the drug in the final product.
ICH M7-Compliant Impurity Testing Strategy
Aligned to ICH M7(R2), we initiate the assessment with QSAR analyses, unless the impurity is already known to be mutagenic, which makes this analysis step unnecessary.
If:
• Structural alerts are identified
• Genotoxicology positive outputs are concluded based on data analysis
Then genotoxicology testing or control measures are required according to ICH Q3A(R2) and ICH Q3B(R2). This could be assessed with an Ames test, and if positive, this could be combined with a purge or further hazard assessment using another genotoxicology assay.
Detection of NonGenotoxic Carcinogens
To address carcinogenic risk beyond direct DNA damage, we offer:
• Bhas 42 cell transformation assay
This assay is a valuable tool for identifying nongenotoxic carcinogens and complements traditional genotoxicity testing strategies.
Customized Testing for Your Discovery Needs
We also provide customized in vitro genotoxicity testing to support early discovery, lead selection, and nonclinical safety assessment.
We offer an integrated early screening battery combining:
• DNA Damage Repair assays
• nanoAmes test (Ames test requiring very low quantities of compound)
• in vitro micronucleus assay
These assays can be strategically combined with QSAR (in silico genotoxicity prediction) to enable rapid, cost-effective identification and prioritization of genotoxic hazards.
Our flexible genetic toxicology testing solutions can be delivered as:
• fit-for-purpose screening assays
• early discovery and lead-optimization tools
• mechanistic genotoxicity investigations
Study designs are fully customized to meet your:
• late Optimization screening
• mechanistic and mode-of-action elucidation
• nonclinical and regulatory strategy requirements
Your Partner for Discovery lead selection and Regulatory-Ready Genotoxicity Assessment
With GLP-compliant execution, regulatory-compliant study designs, and deep regulatory expertise, we support pharmaceutical and biotech companies in building robust, submission-ready genotoxicity packages for global development programs.
Do you have questions about your genotoxicity testing needs?
I would be happy to help you select the right analytical and testing services for your needs. Together, we will find the optimal solution for your requirements. With expertise, a personal approach, and reliable support.
Lars Erlandsson
Sales Manager
+49 152 225 070 24
✔ Personal consultation
✔ Fast response times
✔ Tailored solutions for your project
Our Test Methods:
In-Vitro Genotoxicology
- In-Vitro gene mutation study in bacteria: Ames Test
- OECD 471 / ICH S2
- In-Vitro gene mutation study in mammalian cells: Mouse Lymphoma Assay (MLTK Assay)
- OECD 490 / ICH S2
- In-Vitro gene mutation study in mammalian cells: HPRT test
- OECD 476 / ICH S2
- Micronucleus Assay In-Vitro (Human Lymphocytes or V79 cells)
- OECD 487 / ICH S2
- Fluorescence In Situ Hybridisation (FISH)
- Chromosomal aberration Assay In-Vitro (Human Lymphocytes or V79 cells)
- OECD 473 / ICH S2
- Hen’s Egg Test – Induction of Micronuclei (HET-MN)
- COMET Assay in different cell types
In-Vitro Detection of non-genotoxic Carcinogens
- Cell Transformation Assay in Bhas Cells
- OECD GD 231 (draft)
In-Vivo Genotoxicology
- Mammalian Erythrocyte Micronucleus Test
- OECD 474 / ICH S2
- Combined Mammalian Erythrocyte Micronucleus Test with concurrent Alkaline Comet Assay In-Vivo
- OECD 474 & 489 / ICH S2
- In-Vivo Mammalian Alkaline Comet Assay (several organs on request)
- OECD 489 / ICH S2
- Mammalian Bone Marrow Chromosomal Aberration test
- OECD 475 / ICH S2
The experienced and highly committed GBA Group team offers a variety of different services the following in Areas:
Frequently Asked Questions (FAQ) – Genotoxicity Testing
What is genotoxicity and why is it important in drug development?
Genotoxicity refers to the ability of a substance to damage genetic material, which may lead to mutations, or DNA breakage, and/or may induce tumors. Regulatory authorities require genotoxicity testing to ensure that drugs and impurities do not pose an unacceptable carcinogenic risk before starting clinical studies or commercializing them.
Which genotoxicity studies are required for IND/NDA, PMDA and CTA submissions?
For US FDA Investigational New Drug (IND)/New Drug Application (NDA), PMDA and EMA Clinical Trial Application (CTA) submissions, genotoxicity testing must comply with ICH S2(R1). This typically follows one of the two options (ie 3 combined assays performed with the active substance).
When are genotoxicity studies required during clinical development?
According to ICH M3:
• an Ames test is required before single-dose clinical trials
• an additional in vitro chromosomal aberration or micronucleus test is required before multiple-dose trials
• completion of the full ICH S2(R1) test battery is required before Phase II clinical trials
Do you offer screening genotoxicity studies?
Yes. All genotoxicity studies are conducted in our laboratories, and an expert team supports you regarding the best candidate selection. To accelerate your research, you can rapidly gain early insight into the genotoxicological profiles of your drug candidates during the Lead Optimization and Preclinical phases. By leveraging our expert team and an efficient screening strategy that integrates in silico and in vitro approaches, you can prioritize compounds earlier, reduce attrition, and streamline your discovery pipeline.
Do you offer GLP-compliant genotoxicity studies?
Yes. All genotoxicity studies are conducted in our GLP-certified laboratories and include traceable, submission-ready documentation suitable for global regulatory filings. To further support rapid progression toward regulatory milestones, we design and execute a complete set of ICH-compliant in vitro genotoxicity studies. These core studies can be strategically complemented by additional in silico, in vitro, and in vivo assays, selected according to your therapeutic area and aligned with current best practices, ensuring robust data generation while maintaining speed and flexibility.
Can you support regulatory strategies worldwide?
Absolutely. Our study designs, execution, and reporting are fully aligned with all regulatory expectations, including ICH S2(R1), ICH M3, ICH Q3A(R2), ICH Q3B(R2) and other local guidance documents.
Do you provide testing for drug impurities?
Yes. We support the assessment of mutagenic impurities in accordance with ICH M7(R2), including:
• in silico QSAR assessments
• bacterial reverse mutation tests (Ames test)
• additional in vitro or in vivo testing, when required
Are new alternative approaches (NAMs) to animal testing available?
Yes. In line with the 3R principles, we offer and continue to develop innovative vitro test systems, such as the Hen’s Egg Test on the induction of Micronuclei (HET-MN), to reduce or replace animal testing, when scientifically and regulatory acceptable.
Do you offer cutomized genotoxicity assays?
Yes. We customize study designs of many of our in vitro genotoxicity assays to address specific scientifc or regulatory questions, including testing materials or leachable materials of medical devices (according to ISO 10993-3). We adapt our testing conditions to the therapeutical modalities.
Can you support dose confirmation and exposure analysis?
Yes we provide:
• Dose confirmation analyses using methods validated according to ICH Q2(R2)
• Target organ exposure analyses using methods validated according to ICH M10
Can you help interpret genotoxicity results and support regulatory discussions?
Yes. Our team of genetic toxicologists provide expert interpretation, risk assessment, and scientific justification, and can support regulatory interactions and responses related to genotoxicity findings.
