The EMEA's Committee for Medicinal Products for Human Use (CHMP) has released a list of requirements for a two-month public consultation period, after having extensively investigated the serious adverse reactions that occurred during the first-in-man trial of TGN1412.
The guideline, which has been prepared by experts in clinical trials, is one of the measures taken by the CHMP and EU national authorities to minimise the risk of such serious adverse reactions occurring in the future.
It focuses on potential high-risk medicinal products - drugs where the mode of action, the nature of the target in the body or the limited relevance of animal models for the prediction of toxicological effects in humans raises concerns of serious adverse reactions during first-in-man clinical trials.
In addition, the document gives guidance on handling the transition from non-clinical studies, such as animal or in vitro studies, to first tests in humans for this specific type of drugs.
The committee's proposals also cover quality, non-clinical and clinical aspects, including the calculation for the first doses to be given to human subjects, the initial dose-escalation trials and the management of risk.
Furthermore, one of the requirements relates to the immediate as well as long-term monitoring of adverse reactions.
According to the proposals, a clinical trial should be designed with a specific plan for monitoring adverse events or adverse reactions, with clinical trial staff trained to identify those reactions and how to respond to such events.
This draft guideline comes on the heels of a report published earlier this month which called for reforms in first-in-man clinical trials.
The proposals for reform set by the UK's Royal Statistical Society (RSS) were aimed at minimising drug trial risk, maximising design efficiency and improving protocol review.
21 recommendations for improvement were made in the RSS report surrounding three key areas: risk assessment and communication; preparatory preclinical work; and experimental design, with particular attention to dosing.
Sparking the scrutiny were the events that surrounded a Phase I trial of TGN1412, a monoclonal antibody (mAb) that was being developed to treat chronic inflammatory diseases and leukaemia.
Six out of eight men involved in the trial experienced a severe and systemic adverse reaction and were admitted to intensive care with hours of taking the experimental drug.
Those that were unaffected had been given placebo.
Two firms were in the eye of the storm that followed - TeGenero, a small German biotech firm who developed the drug, and Parexel, an international contract research organisation (CRO) which carried out the Phase I trial on behalf of TeGenero.
Both companies were cleared of any blame in a subsequent MHRA investigation, however, TeGenero has since gone bankrupt and Parexel could face lawsuits from victims.