TGN1412: Joint Industry Taskforce produces guidelines to improve conduct of early stage clinical trials.

Recommendations to enhance and clarify the existing guidelines governing the testing of new medicines in humans following the TGN1412 clinical trial at Northwick Park have been proposed by a joint taskforce set up by the Association of the British Pharmaceutical Industry (ABPI) and the BioIndustry Association (BIA).

The taskforce has highlighted aspects of those guidelines that are particularly important for the very small proportion of clinical trials in which novel agents stimulating the immune system are given to humans for the first time.  Specific recommendations include: Use of an alternative initial dose-setting assessment for certain novel agents; Giving only one subject the active medicine on the first day; Following this with ‘staggered dosing’ as doses are increased; Conducting such studies at a hospital with intensive care facilities; Providing all investigators with appropriate training in such studies; Giving particular emphasis to manufacturing controls to ensure safety, quality and efficacy of the finished product.

Executive Summary

A joint taskforce was set up by the BioIndustry Association (BIA) and the Association of the British Pharmaceutical Industry (ABPI) to provide industry input to the expert working group set up to learn from the TGN1412 clinical trial adverse events at Northwick Park.

Industry was deeply shocked both by the severity of the adverse reactions experienced by the volunteers, and because such an occurrence is without precedence in this country. We would like to express our continuing concern and support for those affected by the TGN1412 trial and our commitment to ensuring that no clinical trial
participants are ever again placed in this situation. The expert group stands ready to assist the regulators by sharing their knowledge and experience. We believe this document will be helpful to all those involved in the clinical development of these novel products and therefore recommend this report to Professor Gordon Duff.

The BIA/ABPI industry taskforce was co-chaired by Dr David Chiswell and Sir Colin Dollery, with its membership consisting of bioscience and pharmaceutical industry experts in fields such as immunology, biopharmaceutical development and clinical trials.

The taskforce considered the same areas as Professor Duff’s expert group which is reviewing early stage clinical trial design with specific reference to:

• biological molecules with novel mechanisms of action;
• new agents with a highly species-specific action; and
• new drugs directed towards immune system targets.

The ABPI and BIA have compiled a detailed “points to consider” document appended to this executive summary and recommendations, and would be happy to provide further input into any discussions on improving guidelines for molecules covered by
the terms of reference of the expert committee chaired by Professor Duff