Overview
• Introduction to the guideline
• Lhasa Limited software tools• Vitic
• Derek Nexus
• Sarah Nexus
• Mirabilis
• Setaria
• Questions
What is ICH M7?
• “Assessment and Control of DNA Reactive (Mutagenic)
Impurities in Pharmaceuticals to Limit Potential
Carcinogenic Risk”
identification
qualification
categorisation
Control of mutagenic impurities to limit potential carcinogenic risk
https://www.ich.org/page/multidisciplinary-guidelines
The ICH M7 Guideline
• Regulatory agencies will accept results from (Q)SAR
methodologies in lieu of in vitro testing.
• These methodologies can be used to support the
decision making for determining mutagenic potential
of impurities and thereby minimising the expense of
testing.
• Expert review is a crucial step, allowing you to justify
your case.
• Experts can make use of existing data to support
decisions and submissions.
https://database.ich.org/sites/default/files/M7_R1_Guideline.pdf
Vitic
Vitic
Two main approaches to toxicity prediction:
Statistical model –
Machine Learning
Algorithm
OH
S
O
O
O
ONH
2
8.2
Expert system –
Rules
Human
expert
Derek Nexus
Sarah Nexus
ICH M7 guidelines allows for in silico purge arguments
Mirabilis
In silico workflow under M7
Expert Review
2 in silico predictions
expert + statistical
Evaluate drug substance, impurities,
degradants, intermediates, etc
Databases, in-house,
literature
Known
mutagen
Both predict
positive
Both predict
negative
Ames testLimit according to TTC or
present purge argument for loss
Treat as non-
mutagenic
Known
non-mutagen
Disagree / fail
to predict
Setaria
• A single point of truth across your organisation
Any questions?