FAQs on Genotoxic Assessment for Impurities

Have you done an assessment of impurities in Drug Substances (API) and Drug products?

ICH M7 recommends the assessment of actual and potential impurities. The assessment involves the database and literature searches for carcinogenicity and mutagenicity of impurity compounds Based on the assessment the impurities should be classified as:

Class 1. Known mutagenic carcinogens.
Class 2. Known mutagens with unknown carcinogenic potential
Class 3. Alerting structure, unrelated to the structure of the drug substance; no mutagenicity data.
Class 4. Alerting structure, same alert in API molecule (or compounds related to API) which have been tested and are non-mutagenic.
Class 5. No structural alerts or alerting structure with sufficient data to demonstrate a lack of mutagenicity or carcinogenicity.

 We offer Scientific Solutions for the Assessment and classification of API and Dug product impurities.

What are the actual and potential impurities?

Actual and potential impurities that are likely to arise during the synthesis and storage of API, and during the manufacturing and storage of a Drug Product.
The assessment is a two-stage process:
Actual impurities (included in the specification) that have been identified should be considered for their mutagenic potential.

Potential impurities likely to be present (Not included in the specification), the evaluation of their mutagenic potential is also required
Actual impurities include those observed in the API above the ICH Q3A reporting thresholds Potential impurities in the drug substance can include starting materials, reagents, intermediates, and by-products observed in the route of synthesis.

Also, degradation products observed during storage (long-term stability conditions) in API and Drug products should also be considered as actual.

Potential degradation products include those observed above the identification threshold during accelerated stability studies (e.g., 40°C/75% RH for 6 months) and confirmatory photo-stability studies.

How do carry out the assessment and classification of all impurities (actual and potential)?

The genotoxic hazard assessment should be done by database search followed by Quantitative Structure-Activity Relationships (QSAR) that focus on bacterial mutagenicity predictions should be performed. This assessment will help to classify all impurities as per ICH M7 (Class 1 to 5).

 We provide computation toxicological tools for the genotoxic assessment of impurity compounds in line with the requirement of ICH M7.

What is the approach for Genotoxic Assessment?

A computational toxicology assessment should be performed using (Q)SAR methodologies that predict the outcome of a bacterial mutagenicity assay. Two (Q)SAR prediction methodologies that complement each other should be applied.

We use two (Q) SAR Software as per the recommendation given by ICH M7.
1. Statistical-Based Models
2. Expert Rule-Based Models

By utilizing the combined software platforms, we can predict potential toxicity for most toxicological endpoints, including Carcinogenicity, Mutagenicity, and Genotoxicity. Regulatory agencies will accept results from (Q)SAR methodologies in lieu of in vitro testing. The report of the assessment is helpful to justify the specification and limits of all impurities.

VEEPRHO has extended its support.

With our service, you can:

  • Ensure the appropriate classification of Genotoxic and Non-Genotoxic Impurities.
  • Avoid Regulatory Observations on Specification Limits of Impurities

Contact us for Genotoxic Assessment Services


Request a quote

"*" indicates required fields

Products quotation