Module 9 2021

19/03/2021

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

7

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

The Organisation for Professionals in Regulatory Affairs

7

Considerations Before Preclinical and Clinical Studies

Before studies are initiated, certain considerations need to be made ● Mechanism of Action (MOA) – Is there 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 patients 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?

8

The Organisation for Professionals in Regulatory Affairs

8

4