First in human (FIH) studies in healthy subjects and patients mark an exciting step for researchers as they move closer to demonstrating the safety and efficacy of new drugs. To help ensure the safety of these participants, the European Medicines Agency (EMA) is updating its guidance for FIH studies, to give sponsors clearer guidelines as they make this transition.

The decision to update the original guidance document came about in May, 2016, following the tragic death of a volunteer during a Phase I FIH clinical trial in France earlier that year. Five other volunteers were also hospitalized in the incident. Interestingly, the current guideline for FIH studies, which was published in 2007, came about in the aftermath of a another tragedy in 2006 in London, when six volunteers were hospitalized with severe adverse events after receiving a monoclonal antibody for the first time. The updated document will offer insights into how to address risk factors for new investigational drugs, quality issues to monitor, potential testing strategies, and advice on trial design for FIH studies. It is also expected to include guidance on starting dose calculations, dose escalation, and criteria for a projected maximum dose based on exposure and related potency. It is a timely update for this guidance document as advances in new technologies related to analytics are now used to proactively track trial data in real time, making it possible for researchers to utilize emerging safety, PK and PD data in real time. This enables better and safer decision making during study progression.

All of the proposed changes to the guidance document were outlined in a draft guidance paper that EMA released last year, which collected more than 600 pages of comments from Contract Research Organizations (CROs), academic institutions, investors, and other industry stakeholders before the comment period closed in February. The high rate of response to the EMA’s concept paper demonstrates just how invested the industry is in protecting the safety of these volunteers and the rigor of these complex early phase studies.

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Sponsors following this development should note that this document is a guidance, which provides information on best practice for safely conducting FIH trials as part of the drug development lifecycle.

It can also be a valuable tool to gauge when to have conversations with regulators, particularly if the trial requires a different approach, based on the profile of the molecule or trial outcome goals. Having these conversations proactively with the regulators can help sponsors communicate their scientific rationale for their proposed departure from the guidance.

While the guidance has not yet been released (as of April, 2017), it is in the final phase of revisions and is expected to be published shortly. In the meantime, sponsors can benefit from reading through the draft guidance, and to take note of how this guidance may impact on their current practice.


> This post was co-authored by Laurence Levasseur, Senior Director of Pharmacokinetics at QuintilesIMS