Genotoxic impurities (GTIs) and nitrosamines are substances that can pose a risk to human health due to their potential to cause DNA damage and increase the risk of cancer. The services on Genotoxic impurities and Nitrosamine assessment in pharmaceuticals and other products have become a significant focus for regulatory authorities and the industry in recent years. Several services are available to support companies in the evaluation and management of genotoxic impurities and nitrosamines.
- Genotoxicity Assessment of Impurities and their classification as per ICH M7.
- Purge factor assessment of Toxic compounds (Genotoxic Impurities, Nitrosamine, and Their precursors).
- Investigation and control of Nitrosamine with International Scientific Support.
- TD50Values of Nitrosamines: Computational approach for determination of carcinogenicity.
Contact our team to carry out Assessment Services for Genotoxic Impurities and Nitrosamine.
Genotoxicity Assessment of Impurities and their Classification as per ICH M7
Our computational toxicology services comprise (Q)SAR methodologies as per the recommendation of ICH M7, for the prediction of bacterial mutagenicity of impurities.
We use two (Q)SAR Software:
- Statistical-Based Models.
- Expert Rule-Based Models.
By utilizing the combined software platforms, this assessment will help you identify the class of impurity in line with the requirements of ICH M7 guidelines. For example, if the impurity is categorized as class 4 or 5 then you can assign the specification limit (as per ICHQ3A/).In case any impurity is categorized as classes 1, 2, and 3, then the impurity limit should be reduced to meet the requirement of ICH M7 in the final specification.
Regulatory agencies will accept the results of (Q)SAR methodologies instead of in vitro testing. The assessment report provided will also help you give justification for specification in the eCTD dossier.
Purge factor assessment of toxic compounds (Genotoxic Impurities, Nitrosamine, and their precursors)
We offer services on Computer Assisted Control Strategy for Genotoxic & Nitrosamine impurities, in line with the requirements of ICH M7 & FDA guidance.
If your Drug Manufacturing Process involves the use of highly reactive reagents, their reactivity can lead to the formation of mutagenic process impurities and Nitrosamine, if they are not removed efficiently. We can support the precise assessment of the removal of such material using computer-assisted tools.
Traditional paper-based purge assessment is not specific and is always questionable by regulatory authorities. A computer-assisted tool allows for a rapid, reproducible semi-quantitative measure for risk assessments of mutagenic impurities and Nitrosamine.
The Final Assessment Report includes:
- The purge calculation.
- Scientific rationale.
- Supporting evidence to aid in the submission to regulators.
The assessment report can save substantial amounts of time and resources without increasing risk to patients.
Investigation and control of Nitrosamine with International Scientific Support
At Veeprho we have an association with a US-based leading international scientific consulting firm in this area. In the past couple of years, the firm has provided consulting related to N-nitrosamine impurities to numerous pharmaceutical companies worldwide. These include risk assessments, queries from regulatory authorities, and strategies for reducing the formation of Nitrosamines in formulated products.
Our Investigator will help and guide you on how to deal with nitrosamine for every stage during formulation development, bio-batch or commercial batches.
- During Synthesis of API and during formulation development.
- At the time of the pilot batch.
- At the stage of bio-batch.
- Or after CMC+Bio means after completion of the dossier before submitting it to FDA.
TD50Values of Nitrosamines (Computational approach for determination of carcinogenicity)
(Q)SAR modeling between structure and carcinogenicity can be used for determining the TD50 value directly. This SAR technique identifies activating or mitigating features based on analogs/surrogate chemicals.
In the current scenario, having a lack of experimental data for NDSRIs, the FDA is aware of this as an alternative approach and this has already been adopted by many innovating companies.
Once the TD50 value is determined, it will help to justify the higher level of nitrosamine impurity in API & Drug Products.
Our global experts will support you if any query is received from FDA on the submitted report.
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