Spring Intro 2023

22/03/2023

Are Toxicology Studies Human (Translationally) Relevant?

⌘ When development is stopped, the true human relevance of toxicity may never be tested

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What’s New in Safety Evaluation?

1. Increasing emphasis on safety in Discovery - lead optimisation 2. ICH S12 Nonclinical biodistribution considerations for gene therapy products . Mar 2023 3. ICH E14 S7B Q&A Q&A Clinical & Nonclinical evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential. Can thorough QT clinical study be avoided ? Feb 2022 4. ICH S1B (R1) Testing for Carcinogenicity - Weight of evidence assessment on the value of 2 yr rat Carcinogenicity test Aug 2022 Non-genotoxic carcinogens – may be more human relevant than envisaged? 1. Ultra-Rapid development of skin cancer in patients, following treatment with B-Raf kinase inhibitors 2. Mecasermin recombinant IGF1 - increased tumour risk in children 3. Ingenol mebutate sap of milkweed plant – increased risk skin tumours at application site See http://www.ich.org 5. ICH M7 (R2) Assessment and control of DNA reactive impurities in pharmaceuticals . addition of 7 new compounds to addendum Oct 2021

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