Module 9 2024

03/09/2024

First-In-Human Studies

• Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products (CHMP; 2017*) • Covers all chemical and biological IMPs, excludes advanced therapy medicinal products (ATMPs) • Highlights the responsibility of the Sponsor to evaluate any associated risks and develop mitigation plans • A step wise approach to reducing the uncertainty of an IMP by gathering knowledge via well designed studies • Outlines the importance of relevant preclinical studies to reduce the level of uncertainty for FIH studies

The Organisation for Professionals in Regulatory Affairs

* EMEA/CHMP/SWP/28367/07 Rev.1

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Considerations Before Preclinical and Clinical Studies

• Before studies are initiated, certain considerations need to be made • Mechanism of Action (MOA) • Is there any precedent of products with this MOA (i.e. established experience) or is this a completely new MOA? • Are the effects likely to be reversible or irreversible? • Are there likely to be effects on- or off-target, downstream? • The potential PK/PD profile and could this be impacted by the patient’s health status? • Is there a suitable animal species to conduct the preclinical studies? • Immunogenicity • Is there the potential for anti-drug antibodies (ADAs) following administration of the product? • If an antibody response is expected, will this impact the PK/PD or safety profile of the product? • Could an antibody response be monitored or reduced in patients?

The Organisation for Professionals in Regulatory Affairs

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