Module 5 Presentations

16/07/2024

Biotech Derived Products Reproductive/developmental toxicity

TAILOR THE PROGRAM FOR THE PRODUCT UNDER DEVELOPMENT

• Where rodents & nonrodents are relevant species; one species, embryo-fetal development (as per ICH S5) if appropriate justification provided • An appropriate ReproTox assessment with the clinical candidate preferred over studies with homologous product  Sponsor can provide scientific justification for alternative approaches including use of surrogate products (ie. One that is designed for the animal species rather than for humans) • Enhanced Pre/Postnatal Development study in Primate is acceptable  Treat NHP during gestation; battery of postnatal obs on offspring  Control group and one treatment group may be acceptable with justification • Non-monoclonal antibody products may have specific timing needs  Potential issue related to placental transfer

The Organisation for Professionals in Regulatory Affairs

Module 5 Lecture 3 – Nonclinical safety assessment

31

CARCINOGENICITY (ICH S1 A-C)

Completed carcinogenicity studies are NOT usually needed in advance of the conduct of clinical trials unless there is cause for concern • For example....

• chemical class effects, prior knowledge • preneoplastic changes in repeated dose toxicity studies • long-term tissue retention of parent or metabolites • genotoxicity (for chronic administration) •

For pharmaceuticals developed to treat certain serious diseases (oncology, HIV), carcinogenicity testing, if needed, may be concluded post-approval. Also not usually required for products intended for single or periodic use. • Alternative models (genetically modified mice)

• Increasing popularity and for investigations and special cases

The Organisation for Professionals in Regulatory Affairs

Module 5 Lecture 3 – Nonclinical safety assessment

32

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