Spring Intro 2023

22/03/2023

Outline: A Carcinogenicity Study

● Use Rats & Mice, 50+/sex/group or transgenic mice 25/sex/group 6months ● Dose: 25/50-fold human exposure (AUC) or the maximum tolerated ● Treat for 2 years, or until 20% survival ● Do histopathology to look for tumours in 40 + tissues per animal, i.e. 16,000+ tissues ● Tables tumour incidence & multiplicity ● Statistical analysis of tumour incidence with weighted survival adjustment ● Results “can delay regulatory review or even be a showstopper”

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Safety Testing of Biopharmaceuticals and Advanced Therapy Medicines …. is Different!

1. Biopharms: use pharmacologically responsive species – in vitro/vivo data to support choice. 2. Tox studies up to 28 days: if possible use 2 responsive species, 1 species for 3 or 6 mo studies. Studies may not be fully GLP compliant 3. Studies in transgenic mice with homologous proteins, or in animal disease models may be appropriate 4. If molecule is potentially immunogenic, take plasma samples to allow measurement of Ab formation. 5. Metabolism studies not needed for Abs & peptides 6. If primate reprotox needed: combine studies of foetal & postnatal development. 7. Carcinogenicity studies: “ weight of evidence ” assessment to determine risk. May be able to label for risk, without doing study . 8. Gene therapy & nucleic acid-based therapies – an individual approach

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