lhasa and the ich m7 guideline and the ich … · methodologies in lieu of in vitro testing. •...

Lhasa and the ICH M7

Guideline

Sales Manager

Krishan.Patel@lhasalimited.org

Krishan Patel

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?