Strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products - Scientific guideline

This document addresses non-clinical and clinical issues for consideration prior to the first administration of an investigational medicinal product in humans. It also addresses the design and conduct of early clinical trials, including trials with integrated protocols. Emphasis is put on defining the uncertainty associated with the medicine tested at each step of the development and describing how the potential risks that might arise from this uncertainty will be addressed. The revision was made in cooperation with the EU Clinical Trials Facilitation Group (CTFG), now known as the  Clinical Trials Coordination Group.

Keywords: First-in-human, phase I, early clinical trials, investigational medicinal product, risk mitigation, integrated protocols, multiple ascending dose, dose escalation

Current effective version

Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products - Revision 1

AdoptedReference Number: EMEA/CHMP/SWP/28367/07 Rev. 1Legal effective date: 01/02/2018Summary:

This document addresses non-clinical and clinical issues for consideration prior to the first administration of an investigational medicinal product in humans. It also addresses the design and conduct of early clinical trials, including trials with integrated protocols. Emphasis is put on defining the uncertainty associated with the medicine tested at each step of the development and describing how the potential risks that might arise from this uncertainty will be addressed. The revision was made in cooperation with the EU Clinical Trials Facilitation Group (CTFG).

Document history - Revision 1 (current version)

Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products - Revision 1

AdoptedReference Number: EMEA/CHMP/SWP/28367/07 Rev. 1Legal effective date: 01/02/2018Summary:

This document addresses non-clinical and clinical issues for consideration prior to the first administration of an investigational medicinal product in humans. It also addresses the design and conduct of early clinical trials, including trials with integrated protocols. Emphasis is put on defining the uncertainty associated with the medicine tested at each step of the development and describing how the potential risks that might arise from this uncertainty will be addressed. The revision was made in cooperation with the EU Clinical Trials Facilitation Group (CTFG).

Overview of comments received on 'Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products'

Reference Number: EMA/CHMP/853503/2016Summary:

Overview of comments received on 'Guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products' (EMEA/CHMP/SWP/28367/07 Rev. 1)

Draft guideline on strategies to identify and mitigate risks for first-in-human and early clinical trials with investigational medicinal products - Revision 1

Draft: consultation closedConsultation dates: 15/11/2016 to 28/02/2017Reference Number: EMEA/CHMP/SWP/28367/07 Rev. 1Summary:

The EMA ‘Guideline on strategies to identify and mitigate risks for first-in-human (FIH) clinical trials (CTs) with investigational medicinal products’ was published in 2007. It mainly addresses the non-clinical aspects of drug development. This reflects the practice at that time which focused on a single ascending dose design. Since then, integration of the non-clinical data available before FIH administrations and the pharmacokinetic, pharmacodynamic and human safety data emerging during a trial has evolved. Consequently, many FIH trials are now performed with integrated protocols potentially combining different study parts. This revision extends the guidance to early phase CTs including single study or integrated protocol designs.

Concept paper on the revision of the 'Guideline on strategies to identify and mitigate risks for first-in-human clinical trials with investigational medicinal products' - Revision 1

Draft: consultation closedConsultation dates: 21/07/2016 to 30/09/2016Reference Number: EMA/CHMP/446302/2016Summary:

Guidance for progression from the conduct of non-clinical studies to clinical trials for investigational medicinal products in humans are addressed in ICH M3(R2) as well as in the EMA ‘Guideline on strategies to identify and mitigate risks for first-in-human clinical trials with investigational medicinal products’ published in 2007. The EMA guideline mainly addresses the non-clinical aspects of drug development and reflects the practice at the time it was developed which focused on a single ascending dose design for first-in-human (FIH) trials. Since then, integration of the non-clinical data available before FIH administrations and the PK, PD and human safety data emerging during a trial has evolved. Consequently, many FIH trials are now performed with integrated protocols potentially combining different study parts. This concept paper outlines aspects to be considered in revising the current guideline to address the evolution of FIH clinical trials protocols.

Overview of comments on 'Concept paper on the revision of the ‘Guideline on strategies to identify and mitigate risks for first-in-human clinical trials with investigational medicinal products’

Reference Number: EMA/CHMP/510967/2016Summary:

Overview of comments on 'Concept paper on the revision of the ‘Guideline on strategies to identify and mitigate risks for first-in-human clinical trials with investigational medicinal products’ (EMA/CHMP/446302/2016)

Document history - First version

Guideline on strategies to identify and mitigate risks for first-in-human clinical trials with investigational medicinal products - First version

AdoptedReference Number: EMEA/CHMP/SWP/28367/07Legal effective date: 01/09/2007

Overview of comments received on the draft guideline on requirements for first-in-man clinical trials for potential high-risk medicinal products - First version

Reference Number: EMEA/295190/2007 Corr.

Draft guideline on requirements for first-in-man clinical trials for potential high-risk medicinal products - First version

Draft: consultation closedReference Number: EMEA/CHMP/SWP/28367/2007 Corr.