Robert A. Bevans-Kerr
Quantitative Interpretation of Genetic Toxicity Dose Response Data for Risk Assessment and Regulatory Decision-making: Current Status, Persistent Challenges, and Emerging Priorities
Co-chairs: Paul White, Health Canada, Ottawa, Canada; Andreas Zeller, Hoffmann-La Roche, Basel, Switzerland
Date: Thursday, December 3, 2020
Time: 9:00AM to 1:30PM EST
Cost: Free to EMGS members; $75 for non-members (non-members can join EMGS for $75 USD)
Registration dates: October 27-December 2, 2020
ABOUT THIS WORKSHOP
The workshop will (1) provide a brief overview of the state of the science regarding quantitative interpretation of genetic toxicity dose-response data, including a brief overview of the BMD combined covariate approach for potency ranking and MOA investigation, (2) a summary of the recent genotoxicity risk assessment case study for the pharmaceutical impurity NDMA, (3) an overview of issues pertaining to developing consensus CES (critical effect size) values for genotoxicity endpoints, (4) a brief overview of issues pertaining to the determination of effective UF/AF values for routine interpretation of in vivo genotoxicity dose-response data in a risk assessment context, and (5) a brief overview of issues pertaining to interpretation of in vitro genotoxicity dose-response data in a risk assessment context. The workshop will conclude with a 90-min structured discussion period aimed at delineating action items and next steps.WORKSHOP AGENDA
Part I – 9:00AM to 10:00AM EST
- Quantitative Analysis of Genotoxicity Dose-response Data for Risk Assessment and Regulatory Decision-making – Where We Are and How We Got Here
15 minutes - Andreas Zeller, Hoffmann-La Roche, Basel, Switzerland
- Existing Paradigm for Use of Gentoxicity Data in Chemical Risk Assessment
15 minutes - Roland Froetschl, BfArM (Bundesinstitut für Arzneimittel und Medizinprodukte), Bonn, Germany
- Establishing Permitted Daily Exposure Values (PDEs) for Genotoxic Impurities in Therapeutic Products – Current Status and Emerging Priorities
15 minutes - Michelle Kenyon, Pfizer, Groton, USA
Break – 15 minutes
Part II – 10:00AM to 11:15AM EST
- Determination of Critical Effect Size (CES) Values for Genotoxicity Endpoints – Current Status and Future Directions
15 minutes - Paul White, Health Canada, Ottawa, Canada
- Empirical Determination of Uncertainty Factors (UFs) for Calculation of HBGVs (Health-based Guidance Values) for Genotoxic Substances
15 minutes - Alexandra Long, University of Toronto, Toronto, Canada
- Genotoxicity Risk Assessment without Animals - Quantitative Interpretation of In Vitro Genotoxicity Dose-response Data in a Risk Context
15 minutes - Marc Beal, Health Canada, Ottawa, Canada
Break – 30mins
Part III – 11:15AM to 12:45PM EST
- Guided discussion with three break-out groups. Each break-out to spend 75min to address 3 questions/issues, i.e., 25 minutes per question
Break – 15mins
Part IV – 12:45PM to 1:30PM EST
- Each of the 3 groups report back – approximately 10min per group
