MHRA Critical Definition Change

On 25-Apr-14, the MHRA issued a press release indicating that the definition of a critical GCP inspection finding had been changed. It now includes ‘Where provision of the Trial Master File (TMF) does not comply with Regulation 31A 1-3, as the TMF is not readily available or accessible, or the TMF is incomplete to such an extent that it cannot form the basis of inspection an therefore impedes or obstructs inspectors carrying out their duties in verifying compliance with the regulations’.
Auditors have faced TMF access problems for many years. Traditional paper TMFs could be retained and spread across several geographical locations due to the structure, or operating systems of the company conducting the clinical trial in question. The result of this logistical challenge was that auditors had to consider whether, additional travel was required, review of the TMF was limited to selected sections only, an artificial TMF (copy of original) was suitable for audit; or to rely on the co-operation of the auditee to be able to obtain and provide any missing documents noted during the audit. None of these options are efficient or effective with regards to time and cost management.
In theory with the introduction of electronic TMFs (eTMFs) a lot of these issues should have been eradicated. However, as most auditors have seen, and to which the MHRA have formally acknowledged, eTMFs can provide a different set of issues to a paper TMF, such as electronic access could not be provided or alternatively only limited access could be provided to inspectors /auditors. The concept of access problems however to a complete TMF is the same regardless of TMF format (i.e. electronic or a paper based) and as a result the essential documents have not been available at the time of audit in order to assess and/or provide assurance that the clinical trial and the quality of data produced has been in accordance with applicable regulatory requirements.
The MHRA decision to elevate the TMF access requirement to a critical GCP Inspection finding will hopefully encourage companies to bring this issue to the forefront and will allow for auditors to be able to conduct audits in an efficient and effective manner in the future, resulting in lower costs to the company.