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Oct 24
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08:30 - 09:00 30 mins
09:00 - 09:10 10 mins
Genotoxic Impurities
Chairperson's Opening Remarks
  • Jeff Kallemeyn - Principal Research Scientist, AbbVie, USA
09:10 - 09:45 35 mins
Genotoxic Impurities
Industry case study: In silico assessment for the control of genotoxic impurities
  • Strategies for using predictive tools to reduce the risk of genotoxicity
  • Exploration of how to improve in silico prediction
09:45 - 10:20 35 mins
Genotoxic Impurities
Practical implementation of ICH M7 - case studies and things to consider
  • Catrin Hasselgren - Computational Toxicologist - Senior Scientist, Genentech, USA
10:20 - 10:55 35 mins
Genotoxic Impurities
Big Data Based Machine Learning Approach for Improving Analog Search for Mutagenicity Prediction
  • Suman Chakravarti - Vice President, Chief Scientific Officer, Multicase

This presentation describes a set of computational methods to identify better analogs for evaluating alerting chemicals during mutagenicity prediction. A novel distributed representation of chemicals fragments was learned from millions of unlabeled chemicals structures and subsequently used for computing chemical fingerprints from structural environments of mutagenicity alerts. The methodology demonstrates the value of transfer machine learning in chemistry. The fingerprints also facilitate automatic mining of mitigating and activating features of mutagenic alerts. Excellent prediction performance was achieved using the distributed fingerprints when compared to traditional binary fingerprints. Additional factors that are relevant in analog based mutagenicity evaluation will also be discussed e.g. how to determine optimal similarity thresholds, number of analogs etc.

10:55 - 11:25 30 mins
Morning Coffee
11:25 - 12:00 35 mins
Genotoxic Impurities
Genotoxic Risk Assessments Supporting Aggressive Pipeline Strategies: Benefits of Purge Factor Analyses on Work Plans
  • Jared Fennell - Principal Research Scientist, SMDD, Portfolio Design and Integration, Eli Lilly and Company, USA

As the pharmaceutical industry attempts to reduce the development timeline to deliver new medicines, the quality and safety of these medicines continue to meet the highest standards. Genotoxic risk assessments incorporated into key positions of the development timeline assist with work plan creation and strategic decisions. Many advantages have been realized using the purge factor methodology to apply appropriate risk on work plans for early and late phase candidates.

12:00 - 12:35 35 mins
Genotoxic Impurities
Applications of the Purge Tool within GSK – Case studies and learnings from Purge Tool usage
  • Neil Stevenson - Senior Investigator, GlaxoSmithKline, UK

Discussion of examples of Purge Tool usage within GSK, sharing learnings and focussing on the following:

  • Conservatism of the Purge Tool approach via comparison to measured data
  • Equivalency of traditional paper-based approach and use of Mirabilis to determine Purge Factors
  • Detail in regulatory submissions in order to share mutagen control strategy
12:35 - 13:10 35 mins
Genotoxic Impurities
The use of kinetics in Option 4 controls
  • Jeff Kallemeyn - Principal Research Scientist, AbbVie, USA
13:10 - 14:30 80 mins
14:30 - 15:05 35 mins
Genotoxic Impurities
The relationship between ICH guidelines for impurities (Q3 & M7) and extractable and leachable (E&L) thresholds
  • Dr. Dvir Doron - Sr. Chemical Toxicologist, Teva Pharmaceutical Industries Ltd., Israel
  • An overview on E&L thresholds
  • How does ICH M7 relate to E&L?
  • Can methods from ICH Q3D be used for E&L analyses?
  • What is the appropriate threshold for unknown E&Ls?
15:05 - 15:40 35 mins
Genotoxic Impurities
ICH Q3D: Elemental Impurities in Topical Pharmaceuticals: A Pragmatic Approach to Calculate Safety Limits
  • Carla Landolfi - Head of WEP Toxicology, Angelini S.p.A., Italy

Elemental impurities in drug products may arise from several sources: they may be intentionally added in synthesis, or may be present as contaminants and consequently detectable in the drug product. ICH Q3D guideline on elemental impurities provides an appropriate process to assess and control elemental impurities in pharmaceuticals. The guideline established oral, parenteral and inhalation Permitted Daily Exposures for each element of toxicological concern. In the present talk it will be presented the pragmatic approach employed in Angelini to set specific safety limits of such potential impurities in the final pharmaceutical formulation.

15:40 - 16:10 30 mins
Afternoon Tea
16:10 - 16:15 5 mins
End of Conference Day Two