The EMEA Guideline on First-in-Human Clinical Trials and Its Impact on Pharmaceutical Development

Abstract

On March 13, 2006, TGN1412, a monoclonal antibody, was administered to humans for the first time. Severe, lifethreatening toxicities ensued. The science behind these adverse events and the immediate responses to this event have been described in another article (Horvath and Milton 2009). The TeGenero incident was a wake-up call to the pharmaceutical industry, the clinical trials community, and the regulatory agencies. The incident was investigated thoroughly by several different groups, including the Expert Group on Phase One Clinical Trials (chaired by Professor Gordon Duff), the Royal Statistical Society, and the Early Stage Clinical Trial Taskforce. Each of these groups issued reports that summarized the causes of the adverse events and proposed ways that such adverse events could be avoided in future first-in-human (FIH) studies (Expert Group on Phase One Clinical Trials 2006; Medicines and Healthcare Products Regulatory Agency [MHRA] 2006; Early Stage Clinical Trial Taskforce 2007; Senn et al. 2007; Royal Statistical Society 2007). At the same time as these reports were being created, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) was working on creating a guideline on strategies to identify and mitigate risks for FIH clinical trials with investigational medicinal products.