There is lingering unease in the biopharmaceutical industry over whether the new arrangements for first-in-man studies of higher-risk compounds put in place by the Medicines and Healthcare products Regulatory Agency may serve as a disincentive to conduct clinical trials in the UK.

However, concerns expressed by the BioIndustry Association about the procedures taking effect this month are not shared by the Association of the British Pharmaceutical Industry, which believes the new mechanism for assessing first-in-man trials will not only work out well but is likely to be mirrored by reforms in other countries.

A recent report in the Financial Times newspaper spoke of “huge regulatory uncertainty” about the arrangements for first-in-man trials in the wake of the disastrous Phase I study with TeGenero’s monoclonal antibody TGN1412. It warned that a number of companies had already delayed their trials or were taking them overseas.

The BIA admitted the story reflected concerns expressed by BIA members in a survey last autumn. At that point, an interim group at the Committee on Safety of Medicines was evaluating Phase I applications for compounds similar to TGN1412. The final report by the Expert Scientific Group on Phase I clinical trials under Sir Gordon Duff was not published until 30 November.

The MHRA now has formal procedures in place for first-in-man trials, with a dedicated Expert Advisory Group and a first committee meeting scheduled for 18 April. Advice on the MHRA website asks sponsors of compounds meeting the definitions of “higher-risk” to make contact with the agency prior to filing for a clinical trial authorisation. The MHRA will then provide feedback on the sponsor’s data package once this has been assessed by the EAG and the new group’s verdict ratified by the Commission on Human Medicines. According to the MHRA, the whole process should take about 30 days.

One year on from TeGenero incident

More than a year on from the TeGenero incident at London’s Northwick Park hospital, though, there still seems to be a “great deal of uncertainty” among BIA members about the arrangements for first-in-man trials, the association says. While the BIA is in discussions with the MHRA and “very much hopes … that any glitches can be ironed out”, it wants reassurances that the new procedure for higher-risk compounds will not be too lengthy or burdensome.

One issue on which the BIA is awaiting conformation is whether the EAG assessment will be able to run in parallel with a CTA application or whether the two steps will have to be followed sequentially. The association is also worried that there does not appear to be a facility for product sponsors to meet directly with the EAG. Dialogue with both the MHRA and the Expert Advisory Group “is what we’d really like to see”, a spokesperson commented.

But the ABPI downplayed the concerns, pointing out that the number of compounds likely to be affected by the new arrangements was “terribly small”. It also questioned the rationale for moving this kind of study abroad, saying other countries were “bound to follow suit”.

The European Medicines Agency’s (EMEA) Committee for Medicinal Products for Human Use (CHMP) recently adopted a draft guideline on requirements for first-in-man trials of high-risk medicinal products. It covers much of the same ground as the Duff report, whose recommendations were taken up in full by the MHRA and the UK government.

While the ABPI acknowledged that the MHRA’s new procedures might be causing some initial concern, it said a lot had been done to address the implications of the TeGenero trial and it believed the EAG procedure was “going to work out well”.

“I really don’t think it’s going to be an issue,” commented ABPI spokesman Richard Ley.