On 15 November 2016, the European Medicines Agency (“EMA”) opened for public consultation its updated Guideline on strategies to identify and mitigate risks related to first-in-human and early clinical trials with investigational medicinal products. The EMA has revised the Guideline, in cooperation with the European Commission and the EU Member States, to further improve the safety of trial participants. The consultation deadline for the draft Guideline is 28 February 2017.

Background

The Guideline initially adopted in 2007 provides advice concerning the safe conduct of first-in-human clinical trials. The Guideline includes advice on the data needed to enable the appropriate design of the clinical trials and to allow the initiation of treatment in trial participants.

The revised Guideline is based on a concept paper that EMA released for public consultation between July and end of September 2016. The concept paper outlined the major areas in the Guideline that required revision to reflect the evolution of practices in the last ten years.

With the revision of the Guideline, EMA aims to further improve the safety of clinical trial participants in the context of increasingly complex trial protocols. The revision is also intended to further assist sponsors in the transition from non-clinical to early clinical development. The revised Guideline identifies factors influencing risk for new investigational medicinal products.

New scope of the Guideline

Under the initial Guideline, first-in-humans clinical trials were associated with a single ascending dose design subsequently followed by a multiple ascending dose clinical trial.

In recent years, the practice for conducting first-in-human clinical trials for new investigational medicinal products has evolved towards a more integrated approach, with sponsors conducting several steps of clinical development within a single clinical trial protocol. This evolution has enabled clinical trial sponsors to assess single and multiple ascending doses, food interactions, or different age groups within integrated protocols.

The revised Guideline identifies strategies for mitigating and managing risks arising from these increasingly complex trial protocols. It lays down principles for the calculation of the starting dose to be used in humans, the subsequent dose escalation, the criteria for maximum dose and principles relating to the conduct of the clinical studies with multiple parts.

The document provides guidance concerning clinical and non-clinical aspects. The section of the Guideline concerning clinical aspects includes guidance concerning the criteria on the basis of which a study should be stopped and the requirement for a rolling review of emerging data with a focus on safety information for trial participants. The document also discusses the handling of adverse events, including the rules guiding progress to the next dosing level.

The section of the Guideline relating to non-clinical aspects includes the better integration of pharmacokinetic and pharmacodynamic data and toxicological testing into the overall risk assessment. The role of non-clinical data in the definition of the estimated therapeutic dose, maximal dose, and dose steps and intervals is also considered.

EMA aims to publish a final revised Guideline for the conduct of first-in-human clinical trials in the first half of 2017.

For further information visit: http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2016/11/WC500216158.pdf