EMEA Recommends Additional Studies for High-Risk Drugs

Sponsors wishing to test new high-risk drugs for the first time in human subjects are advised to conduct additional preliminary studies in some circumstances under a new draft guideline from the European Medicines Agency (EMEA).

The guideline is part of the ongoing regulatory scrutiny prompted by the disastrous Phase I clinical trial of the gene therapy TGN1412 in March 2006, which made six healthy volunteers critically ill and bankrupted the sponsor, TeGenero.

The draft guideline, which is being released for two months of public comment, was developed by the EMEA's Committee for Medicinal Products for Human Use (CHMP). The focus is on high-risk new drugs "where the mode of action, the nature of the target in the human body or the limited relevance of animal models for the prediction of pharmacological or toxicological effects in humans raises concerns that serious adverse reactions may occur," the EMEA said.

The draft guideline recommends that "additional studies to investigate effects in other organ systems should be carried out on a case-by-case basis," over and above the core battery of tests outlined in the CHMP and International Conference on Harmonisation guidelines on "Safety Pharmacology Studies for Human Pharmaceuticals" and "Nonclinical Evaluation Ventricular Repolarization (QT Interval Prolongation)."

The draft guideline singles out drugs targeting the immune system and suggests that "potential unintended effects should be investigated, e.g., through in vitro studies including human material."

The draft guideline can be accessed at www.emea.europa.eu/pdfs/human/swp/2836707en.pdf.