Genotoxicity & Impurities
Genotoxicity risk assessment and evaluation under ICH M7
A complete genotoxicity risk assessment brings everything together: which impurities could be mutagenic, how much is acceptable, and how you will make sure patients are never exposed above that level. We prepare ICH M7 assessments that answer all three questions in a form regulators can review quickly.
- Guideline basis ICH M7(R2) and addendum; EMA and FDA nitrosamine guidance
- Typical inputs Route, impurity list, dose and duration, analytical data
- You receive ICH M7 risk assessment with control strategy
Overview
About Genotoxicity Risk Assessment
ICH M7 sorts impurities into five classes — from known mutagenic carcinogens (Class 1) to impurities with no mutagenic concern (Class 5). Each class has a different approach to setting an acceptable intake: a compound-specific limit, the threshold of toxicological concern (TTC) of 1.5 µg per day for lifetime exposure, or higher less-than-lifetime limits for shorter treatments.
Nitrosamines form a “cohort of concern” and are handled separately. For nitrosamine drug substance-related impurities (NDSRIs), authorities now accept the Carcinogenic Potency Categorization Approach (CPCA), which assigns acceptable intakes from 26.5 to 1,500 ng per day according to structural features. We carry out both the general ICH M7 assessment and the nitrosamine evaluation.
Use cases
When this service helps
New marketing authorisation applications
The ICH M7 discussion expected in Module 3.
Nitrosamine risk evaluation
Identify nitrosamine risks across the product and justify acceptable intakes.
Lifecycle changes
Re-assess when the route, supplier or formulation changes.
Regulatory queries on genotoxic impurities
Provide the classification, limits and control evidence an authority has asked for.
Scope
What the service covers
- Integration of impurity profile, (Q)SAR results and experimental data
- ICH M7 classification of each actual and potential impurity
- Acceptable intake: compound-specific, TTC-based or less-than-lifetime
- Nitrosamine risk evaluation: sources, nitrosating agents, vulnerable amines and packaging
- NDSRI acceptable intakes using established limits or the CPCA
- Control strategy under ICH M7 options 1–4, including purge arguments
- Documentation for Module 3, DMFs and query responses
Who does what
Where confirmatory testing (for example nitrosamine analysis or an enhanced Ames test) is needed, Globaxa specifies it and assesses the results; testing is performed by a laboratory you appoint.
What are the CPCA potency categories?
The CPCA places an NDSRI into one of five categories based on activating and deactivating structural features around the N-nitroso group. Recommended acceptable intakes are 26.5 ng/day (Category 1), 100 ng/day (Category 2), 400 ng/day (Category 3) and 1,500 ng/day (Categories 4 and 5). Compound-specific data can justify a different limit.
What is a less-than-lifetime limit?
For treatments shorter than a lifetime, ICH M7 allows higher daily intakes: for example 120 µg/day for up to one month, 20 µg/day for up to one year and 10 µg/day for up to ten years, compared with 1.5 µg/day for lifetime treatment.
Methodology
How we work
A defined sequence, agreed with you at the start, so you always know what happens next and what we need from you.
- Compile the evidenceImpurity list, (Q)SAR outputs, literature and analytical data.
- ClassifyEach impurity is assigned an ICH M7 class with its rationale.
- Set limitsAcceptable intakes are derived for the dose and duration of treatment.
- Evaluate nitrosamine riskRoot causes are assessed and NDSRI limits set where needed.
- Define controlAn appropriate control option is proposed and justified.
Deliverables
What you receive
ICH M7 risk assessment
Classification, limits and control strategy for all relevant impurities.
Nitrosamine risk evaluation
Root-cause assessment, acceptable intakes and recommended confirmatory testing.
Dossier summaries
Tables and text for Module 2 and 3 or the DMF.
Technical basis
Guidelines we work to
- ICH M7(R2) (2023) and addendumFramework for assessing and controlling mutagenic impurities, with compound-specific acceptable intakes.
- EMA nitrosamine Q&AEU expectations for risk evaluation, confirmatory testing and acceptable intakes, including the CPCA.
- FDA NDSRI guidance (August 2023)Recommended acceptable intake limits for NDSRIs using the CPCA; FDA set 1 August 2025 as the date for confirmatory testing and any required changes.
- FDA nitrosamine control guidance (revised September 2024)Detection and control of nitrosamine impurities in human drugs.
What we need from you
- Route of synthesis and impurity profile (or our impurity profiling report)
- (Q)SAR outputs and any Ames or other genotoxicity data
- Maximum daily dose, treatment duration and patient population
- Excipient, water and packaging information for nitrosamine evaluation
- Analytical methods and results for relevant impurities
Please share confidential information only after an NDA is in place — we are happy to sign one first.
Market and jurisdiction considerations
ICH M7 is applied across ICH regions. Nitrosamine expectations are set by individual authorities — EMA, FDA, Health Canada and others publish acceptable intakes and timelines that are periodically updated. We check the current position for each of your target markets (information current as of October 2026).
FAQs
Genotoxicity Risk Assessment: frequently asked questions
Do you assess nitrosamines in excipients and packaging?
Yes. The risk evaluation covers all plausible sources, including excipients, water, packaging materials and manufacturing conditions.
What if an NDSRI exceeds its acceptable intake?
We help assess options — process or formulation changes, refined compound-specific data or other measures — and document the rationale for the authority.
Can you update an existing ICH M7 assessment?
Yes. We review the current assessment, update it for new impurities, data or guidance, and highlight what has changed.
Talk to us about Genotoxicity Risk Assessment
Share your product, target market and timeline. We will review your requirement and propose a defined scope.
- OfficeFlat no 8-9-3/23/1, Subhash Chandra Bose Colony, Dathunagar, Kanchanbagh, Hyderabad, Telangana 500058, India
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+91 99894 74590 - Emailbd@globaxa.in
- Office hoursMonday to Friday, 10:00–19:00 IST