Potentially mutagenic impurities
Supporting your computational assessment and control of potentially mutagenic impurities (PMIs)
Assessment and control of PMIs
Once a potentially mutagenic impurity (PMI) is identified, in cases when there is no experimental data to support a risk assessment, in silico methodologies can be used to assess the mutagenic potential of impurities under ICH M7.
In line with this guideline, impurities can be classified using in silico tools alongside expert review instead of in vitro and in vivo testing, resulting in a more ethical – through the reduction of animal testing – and cost-effective approach.
Depending on the resulting impurity classification, a control strategy must be defined – considering impurity characteristics and the API process – to limit potential carcinogenic risk and result in chemical safety.
Why choose Consult Lhasa?
Consult Lhasa offer expert risk assessments for potentially mutagenic impurities (PMIs), grounded in the trusted and recognised science of Lhasa Limited. With over 40 years of collaboration with industry and regulatory authorities, Lhasa Limited has been at the forefront of PMI in silico assessment science. This has led to clear alignment with the global impurity guideline, ICH M7.
For assistance with computational assessment and control of your PMIs, Consult Lhasa.
How can our experts help you to assess
potentially mutagenic impurities?
Are you looking for support in classifying the PMIs of your active ingredient, in accordance with ICH M7?
A computational toxicology assessment under ICH M7 is conducted using two (Q)SAR methodologies, which collectively predict the result of a bacterial mutagenicity test. In line with the ICH M7 guideline, we offer a complete toxicological assessment of your PMIs, in relation to your active pharmaceutical ingredient (API). This is achieved using Lhasa Limited (Q)SAR tools – expert rule-based system, Derek Nexus and statistical system, Sarah Nexus – which are aligned with OECD principles. After applying Consult Lhasa expert review – a critical aspect of an ICH M7 submission – we will provide you with an ICH M7 classification for each of your impurities.
Do you know how to define the acceptable limits for your PMIs?
The approach for calculating an acceptable limit varies based on the ICH M7 classification assigned to each impurity. We can assist you in determining the acceptable limits for your impurities.
Do you need help selecting a control strategy for your impurities?
A control strategy must be selected when an impurity is classified as class 1, 2, or 3 in accordance with ICH M7. The ICH M7 guideline offers four potential control strategies, which should be selected based on scientific reasoning. We can evaluate your impurity and process characteristics to propose an appropriate control strategy.
Do you need support justifying your ICH M7 control Option 3 or 4?
If control Option 3 or 4 under ICH M7 is an appropriate control strategy, a purge argument can form part, if not all, of the justification. We can provide a scientifically sound and consistent purge calculation using Mirabilis and the expert knowledge of Consult Lhasa to improve your regulatory submission.
We provide regulatory support
ICH M7
“Our experience with Consult Lhasa has been very positive, resulting in a final report that we are confident will meet the scope required by regulatory agencies. The Consult Lhasa team are knowledgeable about the regulatory needs of the region, particularly Brazil, and provide great support. Their consulting has been invaluable to our company, the technical, scientific and human exchange has been impeccable. We are very satisfied with the collaboration.”
Adriana Tomalino, Head of Regulatory Affairs at Triquim
“We recently had the experience of collaborating with Consult Lhasa to address an EU regulatory deficiency on a potential degradation impurity of the drug substance. Consult Lhasa made an intriguing task look simple in the final report which was based on Zeneth, literature review and expert analysis. Their professionalism and commitment to excellence were truly commendable and their proactive approach made the entire process seamless and ensured that we met the stringent regulatory timelines. Their core scientific knowledge, hands-on experience with the pharmaceutical industry and caliber of their work make them a standout choice. It is evident that they take great pride in what they do, and this pride reflects in the exceptional quality of their work. We strongly recommend Consult Lhasa to anyone seeking expert advice on API degradation profile, drug-excipient compatibility, leachables & extractables, potentially mutagenic and non-mutagenic impurities and most importantly the nitrosamine impurities.”
Muzaffar Khan, Senior General Manager within Regulatory Affairs at Laurus Labs Limited
Get in touch
If you are interested in discovering how Consult Lhasa could improve your potentially mutagenic impurities risk assessments, get in touch.
