On 24th September 2012 the Medicines and Healthcare products Regulatory Agency (MHRA) published a Good Clinical Practice Guide. Containing 542 pages, this is an essential reference book for anyone involved in some way with the conduct of clinical trials of medicines for human use in the UK. In addition to a chapter entitled “Key Trial Documentation” (chapter 4), it has a whole 29 pages devoted to the trial master file and archiving (chapter 10).
There are no great suprises in the guide. However, the guide states very clearly in black-and-white the MHRA viewpoint on many of the issues that have caused controversy and discussion over the years. I have picked out just a few examples to whet your appetite:
- The contents of the TMF should be sufficient to adequately reconstruct the trial, along with key decisions
- The TMF will be more than just the documents identified in ICH GCP as essential documents
- Signatures are only recommended where they add value. The guide also acknowledges that wet-ink signatures are usually just down to internal requirements; if your SOPs don’t mandate that a signature is required, it is likely that your documents don’t need to be signed!
- Ideally, the TMF should be a stand-alone set of documents rather than distributed across different file systems or electronic systems
- Emphasises the need for a document management plan when using a CRO
- Describes the inspectors’ expectations for “maintaining the TMF in a timely manner”
- Emphasises the unacceptability of an electronic Investigator Site File (eISF) to be held by the sponsor at the end of a trial which the site accesses via a portal (the ISF must be controlled by the site)
- Describes what is meant and required by QC of scanned images
- Describes the requirements of an electronic trial master file (eTMF)
- Confirms that destruction of original records following scanning is not ruled out, subject to several caveats
I think this will become an indispensable guide for the clinical records manager, clinical trial administrator and others involved in clinical trial activities. At £45, it may be beyond some budgets so I’d recommend getting a copy for your organization / company and taking a look through. Happy reading!