Genotoxicity & Impurities
Toxicological risk assessment and qualification of impurities
When an impurity exceeds its ICH qualification threshold, or an authority questions a limit, you need a toxicological justification. We prepare focused risk assessments that qualify impurities and degradants, justify limits for solvents and elemental impurities, and answer safety questions raised in regulatory review.
- Guideline basis ICH Q3A(R2), Q3B(R2), Q3C, Q3D; ICH M7 for mutagenicity
- Typical inputs Impurity identity, proposed limit, product dose and duration
- You receive Signed qualification or safety evaluation report
Overview
About Toxicological Risk Assessments
ICH Q3A and Q3B set thresholds above which impurities must be identified and qualified — that is, shown to be safe at the proposed level. Qualification can use existing data, literature, the impurity’s presence in toxicology studies, or a health-based limit. Our assessments document which route is used and why it is sufficient.
We also prepare safety evaluation reports when a reviewer asks a specific safety question, applying the same rigour to a narrower question so that the response is clear and well-referenced.
Use cases
When this service helps
Impurity above the qualification threshold
Justify a specification limit above ICH Q3A/Q3B thresholds.
Degradants in stability studies
Assess new or increasing degradation products.
Residual solvents and elemental impurities
Derive PDEs for unlisted solvents or justify route-specific limits.
Safety queries from an authority
Prepare a safety evaluation in response to a deficiency letter.
Scope
What the service covers
- Review of impurity identity and mutagenicity status (with ICH M7 assessment if needed)
- Toxicological data and literature review for the impurity or close analogues
- Qualification against ICH Q3A/Q3B, including comparison with levels in toxicology studies
- PDE derivation for residual solvents not listed in ICH Q3C
- Elemental impurity limit justification under ICH Q3D, including route-to-route adjustment
- Safety evaluation reports for regulatory queries
Who does what
Assessments use published and client-supplied data. If qualification requires new studies, we specify them; studies are conducted by a laboratory you appoint.
What are the ICH Q3A thresholds?
For a drug substance with a maximum daily dose up to 2 g, the qualification threshold is 0.15% or 1.0 mg per day total intake, whichever is lower. Identification and reporting thresholds are lower. ICH Q3B sets dose-dependent thresholds for degradation products in drug products.
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.
- Define the questionImpurity, proposed limit, dose and duration are confirmed.
- Check mutagenicity firstMutagenic impurities follow ICH M7 rather than Q3A/Q3B.
- Review the dataToxicology for the impurity or analogues is evaluated.
- Conclude and documentThe limit is qualified or an alternative is proposed.
Deliverables
What you receive
Qualification report
Rationale, data and conclusion for the proposed limit.
Safety evaluation report
A focused response to a specific regulatory safety question.
Dossier text
Summary wording for Module 2 and 3 where helpful.
Technical basis
Guidelines we work to
- ICH Q3A(R2) and Q3B(R2)Thresholds and qualification approaches for impurities in drug substances and products.
- ICH Q3CPDEs for residual solvents and the method for deriving new ones.
- ICH Q3D(R2)PDEs for elemental impurities by route of administration.
- ICH M7(R2)Applied first, to separate mutagenic impurities from those assessed under Q3A/Q3B.
What we need from you
- Impurity name and structure, and how it arises
- Proposed specification limit and supporting batch data
- Maximum daily dose, route and treatment duration
- Any toxicology studies in which the impurity was present
Please share confidential information only after an NDA is in place — we are happy to sign one first.
Market and jurisdiction considerations
ICH Q3 guidelines are applied in ICH regions and referenced by many other authorities. Some national pharmacopoeias set specific impurity limits that also have to be met.
FAQs
Toxicological Risk Assessments: frequently asked questions
How is this different from your Toxicological Risk Assessment Reports?
This service qualifies impurities in drug substances and products. Manufacturing questions such as cleaning agents and cross-contamination are covered under Toxicological Risk Assessment Reports.
What if the impurity is mutagenic?
Mutagenic impurities are controlled under ICH M7 at much lower levels. We assess them through our genotoxicity evaluation service.
Can a literature-based qualification be accepted?
Often, yes — provided the data are relevant and adequate. The report explains the data quality and any limitations.
Talk to us about Toxicological Risk Assessments
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