The new rules are designed to prevent a repeat of last year's drug trial disaster and Dr Tim Mant, senior medical advisor for Quintiles' Guys Drug Research Unit in London, hailed the new system as "good news for early-phase clinical research in the UK." Interim arrangements have been in place since May 2006, shortly after the TGN 1412 drug trial incident, and were finally cemented by the Medicines and Healthcare products Regulatory Agency (MHRA) in February this year. A key feature of the new procedure is the review of certain first-in-man trial applications by an Expert Advisory Group (AEG), followed by the Commission on Human Medicines (CHM). April 18 is the date of the first official AEG meeting. The new review process was established on the advice of the Expert Working Group, chaired by Professor Sir Gordon Duff and set up by the Secretary of State for Health, to provide an independent expert review of the TGN 1412 incident. Under the changes, investigatory compounds that are deemed 'high risk' will have five opportunities each year to be reviewed and approved to enter first-in-man trials. The MHRA website lists five dates that specific application data for these compounds must be submitted by, and three weeks after these dates, the AEG, compiled of experts tailored to the specific needs of the applications, will meet to review them. The AEG will then make their recommendations known to the CHM, who will meet the next day to compile a report to submit to the MHRA as to which compounds can and can not be cleared for human testing. After this, the MHRA will respond to the applicant within 14 days regarding their decision. The total process, from data submission to decision, takes six weeks. For the purpose of the new regulations, high risk compounds can fall into one of three categories: a biologic drug with a novel mechanism of action; an agent (usually biologic) which is highly species specific, meaning that there is a high likelihood that the animal model used may not be predictive of the response in man; and/or any new drug that is directed against the immune system. The majority of new compounds will not fit into any of these categories and will therefore remain unaffected. Commenting on the regulations from a contract research organisation (CRO) perspective, Mant told Outsourcing-Pharma.com: "I think this is a very positive thing for the UK, a system has finally been implemented and is now functioning." "We are the first country in the world to take this step and I think this will work in the UK's favour as far as clinical research is concerned." Europe's regulator, the European Agency for the Evaluation of Medicinal Products (EMEA) is currently in the process of issuing a guideline on the matter, which Mant believes will end up very similar to the system implemented by the MHRA, although actual regulations will be up to each individual country, he said. The US Food and Drug Administration (FDA) is less advanced in its dealing with this issue, however, Mant said he suspects the FDA will soon follow suit. "There is a good communication between the FDA and the EMEA on this issue," he said. However, not all those in the industry appear to be happy with the MHRA's new rules. The Financial Times (FT) recently reported that some pharmaceutical groups are warning that the tough new regulations are "driving medical research out of the UK." In particular, Aisling Burnand, chief executive of the BioIndustry Association, was quoted as saying: "There is huge regulatory uncertainty and some companies have already voted with their feet." He said he is now holding talks with the regulator on the subject. Burnand also complained that the MHRA's advice on high risk applications had been contradictory and the approval process will now take "much longer" than the 30-day turnaround time offered by the FDA. According to the FT report, the MHRA had first rejected one of his member companys' arguments that a trial needed to be scrutinised by the new procedures, then was told to file anyway, and finally had its appeal approved. "They don't know what they are doing", he said. Commenting on this, Mant said: "I personally do not agree." "I think the MHRA have come up with an excellent idea and if anything it may attract more research in the UK because we now have a clear, three-step, timed process in place and the process is clearly defined on the MHRA's website and if companies have any questions they can email the MHRA and expect a response within 7-14 days." "I think perhaps some concerns may have been felt during the interim period, but this has now finished." Indeed, according to MHRA data, four first-in-man trials for high-risk drugs had already been approved by the MHRA as of March 2006 but not yet started, and under the interim arrangements put in place between March 2006 and January 2007, these all had to be re-reviewed. As a result, two sponsors chose to conduct them outside the UK; one was approved; and one is still awaiting responses from sponsor. At the same time, four applications had been pending in March 2006 and also had to be assessed under the interim arrangements. As a result, one was approved; one sponsor response was received in March 2007; while two further sponsor responses are still awaited. In addition, four new high risk applications were received during the interim period with the result being that one was subsequently withdrawn by the sponsor; two sponsor responses were received in March 2007; and one response is still awaited, said the MHRA. Commenting further, Mant said that he was aware of a client who during the interim period had chosen to conduct the trial outside the UK because of the uncertainty surrounding timelines, but upon speaking to them since, he is "not convinced" that they managed to get the trial approved any sooner than if they had gone through the interim MHRA process in the UK. "Now that the interim period is over, this client has since indicated to me that they would now come back to the UK to run these types of trials in the future," said Mant. "The UK has a fantastic reputation for early phase research." In addition, Mant said that through the EAG system, sponsors now have access to expert advice on trial elements such as dosing and protocol design very early on in their drug development timeline, which is a "great improvement" on the old process, where sponsors had to first submit an application to the MHRA and after 21 days were often told to "go and get an expert consultation". Since the new system was implemented in February this year, there have been two clinical trial applications judged to be in the high risk category (both acting on immune targets) and both of them will now be considered by this week's EAG.