The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) has published a draft proposal for a voluntary accreditation scheme for clinical trial units (CTUs) conducting Phase I studies.

The scheme, which was drafted by the MHRA’s Good Clinical Practice (GCP) inspectorate, was among the recommendations put forward last November by the final report of an Expert Scientific Group (ESG) on Phase I trials, set up by the UK government in response to the disastrous first-in-man study of TeGenero’s monoclonal antibody TGN1412 at Northwick Park Hospital in London.

The ESG’s report said the development of a national inspection and accreditation system for clinical centres undertaking first-in-man studies of higher-risk new chemical entities “should be encouraged." Accreditation should be “open to all centres that fulfil defined criteria, in both the public and private sectors,” it added. The report also recommended setting up a national professional accreditation system for principal investigators conducting first-in-man clinical trials.

Duff recommendations taken up

The 22 recommendations of the Duff report were taken up in full by UK ministers and the MHRA. The regulatory agency has already acted on some of the recommendations, notably by establishing a dedicated Expert Advisory Group to assess applications for first-in-man trials involving “higher-risk” compounds.

The current draft of the proposal for an accreditation scheme for Phase I CTUs is the second to date. A first draft went out for consultation with representatives from industry, the National Health Service (NHS), academia, ethics committees and the UK Resuscitation Council in December 2006. The GCP inspectorate is now seeking input from the Committee on Human Medicines; it will then further revise the proposal and put it out for public consultation.

The inspectorate has been pursuing routine statutory GCP inspections of units conducting Phase I trials since May 2004, and at the beginning of 2006 it moved to a cyclical inspection programme, the MHRA notes. The aim is to “increase the scope and depth of inspections in order to provide MHRA and Ethics Committees with more information about the facilities and personnel seeking to conduct these trials.”

The proposed scheme would “give assurance that facilities within the scheme meet satisfactory standards for minimising risk to trial subjects and for handling medical emergencies if they arise,” the agency stated.

Classification requirements

The scheme envisaged in the latest draft would apply to commercial and non-commercial units conducting non-therapeutic Phase I and Phase II clinical studies, including early-phase trials in patient populations such as asthmatics. The scheme is not intended “initially” for Phase I studies in terminally ill patients (eg. oncology trials), the document adds. Some of the classification requirements foreseen in the proposal “may not be applicable in these cases, for example palliative care may be more appropriate than rapid transfer to a critical care unit.”

Under the scheme, units carrying out early-phase trials would be classified and accredited as either Type A, meaning they satisfied the requirements for conducting clinical trials with compounds at all levels of risks, including those defined by the MHRA as 'higher-risk'; or Type B, which would be CTUs accredited to perform trials other than first-in-man studies with 'higher-risk' compounds.

Type A Units would have to meet “all of the requirements for managing serious medical emergencies affecting trial subjects,” the draft proposal notes. These would include “robust (and tested) arrangements for immediate maintenance of life support and onward transfer of subjects to hospital.” While physical location within a hospital would not be a prerequisite for Type A status, the expectation would be “that an ambulance could reach the Unit within 15 minutes of a call being placed.”

Inspection fees

CTUs would first carry out a self-assessment and apply for either Type A or Type B accreditation. An inspection would be carried out in accordance with these self-definitions, and with an “appropriate” fee. Fee levels are still under discussion but would need to be higher than those currently levied for GCP inspections, to cover “additional inspection and administrative activities,” the MHRA says.

A request to reclassify from B to A status at a later date would attract an additional fee, “as an inspection will be required to assess criteria not previously reviewed,” the draft proposal points out.

Inspection reports and accreditation certificates would be sent to the relevant ethics committees/National Research Ethics Service (NRES) to “assist them with their responsibility to carry out site-specific assessments of these units.” Despite the voluntary nature of the scheme, non-participating CTUs conducting Phase I trials “may be required to prove their ability to perform first-in-human trials of ‘higher-risk’ compounds prior to trial approval,” the MHRA warns.