An Industry Perspective on the 2017 EMA Guideline on First‐in‐Human and Early Clinical Trials
In July 2017, the EMA released a revised guideline titled “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), following an incident that resulted in one death and serious neurologic outcomes in healthy subjects during a phase I multiple‐ascending‐dose (MAD) CT in France.1 The tragedy prompted industry sponsors to learn from this rare event and to reexamine their processes. Member companies of the International Consortium for Innovation and Quality in Pharmaceutical Development (IQ), Preclinical Safety Leadership Group (DruSafe) published their nonclinical practices on progression of small molecules to early clinical development, and concluded that the then existing nonclinical approaches and guidance, together with science‐based risk mitigation strategies, support safe early CTs.3 Several publications on phase I CT safety support this conclusion.4
While the revised guideline helpfully addresses more recent innovative early CT approaches, the industry view is that the tragic events in France were not a failure of existing guidance, and that the guideline in effect at the time, when paired with sound science and clinical judgment, was adequate to protect human safety. We believe the new conservative guidance will have little added benefit to subject safety in early CTs and may impede drug development. Some recent industry experience suggests the changes are already negatively impacting multiple stages of clinical development in Europe.