The Medicines and Healthcare products Regulatory Agency’s (MHRA) voluntary Phase I Accreditation Scheme went into effect today with the stated goal of formalizing routine inspections and increasing the scope and depth of inspections. Most importantly, the aim of the MHRA’s new scheme is to avoid harm to trial subjects and for handling medical emergencies during first-in-human trials should they arise.

In the wake of the international media attention that TeGenero received in March 2006 after administering TGN1412 to six healthy volunteers who suffered a nearly fatal “cytokine storm,” the UK in particular has intensely scrutinized how first-in-human phase I trials are conducted and how their conduct could be improved. 

In response to the Duff Report, the European Medicines Agency (EMEA) released a new guidance document on strategies to identify and mitigate risks for first-in-human clinical trials with investigational medicinal products. The guideline went into effect September 2007.

Out of the 22 recommendations made by the Duff Report, three fell under the category of “the clinical environment for first-in-man studies” and two under “developing expertise” on the part of clinical research personnel conducting first-in-human clinical trials.

The final recommendation reads, “The development of a national inspection and accreditation system for clinical centres that undertake first-in-man studies of higher risk agents should be encouraged. The accreditation should be open to all centres that fulfill defined criteria, in both the public and private sectors.”...

In response to these five recommendations, the MHRA published its Phase I Accreditation Scheme and began offering voluntary accreditation last month.

The aim of the new scheme is to formalize routine inspections and to increase the scope and depth of inspections to provide MHRA and ethics committees with more information about the phase I units that want to conduct first-in-man clinical trials so that approval decisions can be more informed. The scheme would give assurance that phase I units within the scheme meet satisfactory standards for avoiding harm to trial subjects and for handling medical emergencies should they arise.

It was created to accredit commercial and non-commercial units conducting non-therapeutic phase I studies only, including those units conducting early phase studies in patient volunteer populations, e.g., asthma sufferers.

The MHRA lists 16 requirements related to the handling of medical emergencies, qualified staff in adequate numbers, standard operating procedures and equipment requirements for standard accreditation. Supplementary accreditation has three additional requirements related to investigator training, hospital access, contingency planning and how subjects’ medical history is obtained.

Standard accreditation inspections equate to the current Good Clinical Practice inspections, but supplementary inspections are wider in scope and more detailed. Units must complete an application form and pay fees, consisting of an initial set-up fee and a fee each time a new certificate is issued

The scheme is not intended initially for phase I studies in severely ill patients that are conducted in a hospital setting or to apply to units that only conduct non-drug trials, i.e., those that do not require a Clinical Trial Authorisation (CTA).

The MHRA plans to work with units conducting phase I studies in patients to create an appropriate accreditation scheme for these units.