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. Within this arena, recommendations cover the whole range of the Phase 1 development sequence, from comments and advice on the compound's mechanism of action and biological activity through to the education and training of those involved in safety assessment.
The taskforce recommendations, which are based on existing best practice within industry, have been submitted to the scientific expert group chaired by Prof Gordon Duff reviewing early stage clinical trials. 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. by Prof Gordon Duff reviewing early stage clinical trials.
Specific recommendations include:
Giving particular emphasis to manufacturing controls to ensure safety, quality and efficacy of the finished product.
"As a responsible industry, we were shocked and want to ensure a similar event never occurs again, and that is why we have developed these 'points to consider' for first-in-human clinical studies," said Dr David Chiswell, one of the co-chairmen of the taskforce.
"In order to safeguard patient safety, we want to make the guidelines available to the research-based industry and - if either the UK or the European regulatory bodies find this useful - to help develop them into a more formal set of 'points to consider'."
The taskforce carefully examined existing regulatory guidance for biopharmaceuticals. Said co-chairman, Sir Colin Dollery: "On the one hand, it was clear that there are no major safety-related issues not addressed in the existing guidance - as demonstrated by the fact that there have been tens of thousands of such trials without any major incident.
"However, it was also clear that the specific wording of certain points could be clarified and that some may need greater emphasis, primarily in relation to novel biological agents or medicines based on a novel way of working. Decisions about the first administration to man of agents that stimulate the immune system need especially careful scrutiny."
The ABPI and BIA set up their joint taskforce to provide industry input into Prof Gordon Duff's expert working group established to learn from the TGN1412 clinical trial adverse events. Membership of the group comprised bioscience and pharmaceutical industry experts in fields such as immunology, biopharmaceutical development and clinical trials.
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