Policy responses and statements

Name of organisation:

Medicines and Healthcare Products Regulatory Agency (MHRA)

Name of policy document:

MLX 341: Proposal for a Voluntary Accreditation Scheme for Phase I Clinical Trial Units in the UK

Deadline for response:

12 October 2007

Background: The TGN1412 incident, in March 2006, where six trial subjects became seriously ill and were admitted to intensive care, has raised the profile of phase I clinical trials in general and 'First in human' (FIH) trials in particular.

It is recognised that the recommendations from the Expert Scientific Group (ESG) include procedural changes for the conduct of FIH studies and that European guidance on First in Human studies on Investigational Medicinal Products (IMPs) has been published. The MHRA will also seek the opinion of an Expert Advisory Group for those FIH studies with risk factors that would require review before a clinical trial may be authorised. To create additional public confidence in the regulatory oversight of such trials, it is proposed that a voluntary accreditation scheme be established for units conducting phase I trials in the UK.

The aim would be to formalise routine inspections and to increase the scope and depth of inspections in order to provide MHRA and Ethics Committees with more information about the facilities seeking to conduct these trials, so that approval decisions are made even more robust.

The scheme would give assurance that facilities within the scheme meet satisfactory standards for avoiding harm to trial subjects and for handling medical emergencies should they arise.

The MHRA GCP Inspectorate already carries out GCP inspections of units conducting phase I trials in the UK and, at the beginning of 2006, moved to a cyclical programme of inspeciions of these units.

Scope:

It is proposed that a voluntary accreditation scheme is created for units (commercial and non-commercial) conducting phase I trials. The scheme would have a classification system based on facilities, training and experience of personnel and ability to manage trials with certain risk factors that would require review by the Expert Advisory Group (EAG) to the Committee on Human Medicines (CHM). Further information on these risk factors can be found on the MHRA website and in the CHMP Guideline on strategies to identify and mitigate risks for first-in-human clinical trials with investigational medicinal products.

The scope of the scheme will initially be for units conducting non-therapeutic Phase I studies. These may include those units conducting early phase studies in 'patient volunteer' populations eg asthma sufferers. The proposal is not intended for Phase I studies in severely ill patients. The accreditation scheme is also not intended to apply to non-drug trials ie those that do not require a Clinical Trial Authorisation (CTA).

COMMENTS ON
MEDICINES AND HEALTHCARE PRODUCTS REGULATORY AGENCY (MHRA)
MLX 341: PROPOSAL FOR A VOLUNTARY ACCREDITATION SCHEME FOR PHASE I CLINICAL TRIAL UNITS IN THE UK

The Royal College of Physicians of Edinburgh is pleased to respond to the Medicines and Healthcare Products Regulatory Agency on consultation letter MLX 341.

The College recognises the need for increasingly formal recognition of the suitability of units which carry out phase I clinical trials and broadly supports the current proposals.  In the consultation with Fellows of the College, a number of concerns were identified and these are highlighted below.

1. Given the importance of this area, it is not clear why the accreditation scheme is not mandatory rather than voluntary.  After all, the safety of volunteers participating in phase 1 studies is at issue.

2. It is unclear from the document how the definition of non-therapeutic phase I studies is made, as such studies will include ‘patient volunteer’ studies.  The document outlines examples of ‘novel compounds’ where expert advice may be sought and gives a clear impression that such compounds may be used ‘therapeutically'.  Arguably, the scheme should include both therapeutic and non-therapeutic trials.  It would seem more appropriate if resources allowed that such an accreditation scheme should be implemented initially in therapeutic studies where volunteers are likely to be exposed to higher risk.

3. It could be argued that the standards applied to supplementary accreditation should be applied to the standard accreditation, as the facilities available for the care of patients who suffer an adverse event following a ‘novel’ compound should be similar to those available should a volunteer suffer an adverse reaction to a standard (non-novel) compound, even if the chances of an adverse event are much lower.

4. The criteria for classification (Appendix 1) should identify more clearly the required qualifications, experience or training of medical personnel involved with standard accreditation.  A training record and curriculum vitae are mentioned, but we are not told what should be in them.

Copies of this response are available from:

Lesley Lockhart,
Royal College of Physicians of Edinburgh,
9 Queen Street,
Edinburgh,
EH2 1JQ.

Tel: 0131 225 7324 ext 608
Fax: 0131 220 3939

[10 October 2007]