The MHRA “Gray Guide” – At last, Some Agency Guidance on eTMF

December 17, 2012

  • eTMF Guidelines

On 24th September 2012 the Medicines and Healthcare products Regulatory Agency (MHRA) published a Good Clinical Practice Guide. Currently, the GCP Guide is only available for hard copy purchase, but I understand it will soon be released as an eBook.
The book contains an entire chapter on Trial Master File and archiving – the first detailed guidance that any regulatory authority has issued on this topic. Furthermore, it specifically addresses the subject of electronic Trial Master File (eTMF).

The chapter contains a number of key points relevant to any sponsor or CRO implementing an eTMF. I’ll cover a few key points here, focusing on those that may resolve issues discussed at great length in the past.

  1. Although the TMF must retain all essential documents related to a trial, the documentation “does not necessarily need to be in the same location, but it must be clear as to where it is held from TMF procedures or indexes.” As an example, MHRA cites the possibility of retaining Serious Adverse Event (SAE) cases in the pharmacovigilance department, including SUSAR receipt confirmation, rather than printing off and filing in the TMF.
  2. Touching on another hot topic discussed in our recent post, MHRA discusses the importance of and contents of a TMF plan for trials involving CROs. Elements of this plan might include who holds the official TMF (or portions whereof), filing processes, access and oversight, how the TMF/eTMF would be made available if either party was audited, and what is done with the TMF/eTMF when the trial is completed. MHRA does not dictate a specific “right answer” to how these issues are handled, but stresses planning and documentation of the approach.
  3. MHRA stresses that ICH GCP and EudraLex Volume 10 should not be considered a checklist or Table of Contents for TMF. In fact, they are only a minimum set of documentation that should be considered essential. Any and all documents needed to reconstruct the trial conduct are required to be collected and maintained.
  4. Duplication of documents within the TMF is to be avoided. For eTMF, this implies an approach where a single content file can be indexed to multiple locations.
  5. For eTMF, emphasis needs to be placed on controls, security, training and validation.
  6. MHRA GCP inspectors will require “direct access to the eTMF system (not a copy), without reliance on an eTMF ‘super-user’, so the system should ideally facilitate a read-only ‘inspector or auditor view’ access.”
  7. Records retention (for TMF or eTMF) is a complicated subject that requires taking into account both EC and national requirements for European trials. In addition, a sponsor must design a retention strategy that accounts for sites closing, organizations being acquired, and individuals retiring).

MHRA GCP Gray GuideThere’s lots more. In future posts and white papers, Wingspan’s team will be discussing issues such as handling of correspondence, how you determine essential documents for a trial, and other key issues. In the meantime, if you work with TMF and don’t have a copy of the guide, I would urge you to obtain one, even if you don’t work on European trials. The guidance provided by MHRA is likely to serve as a blueprint for other regions.