The UK MHRA have published a set of Frequently Asked Questions on the topic of Trial Master Files and Archiving. These can be found on the their online forum.
Readers who have purchased a copy of the recently published MHRA GCP Guide (the “grey guide”) will recognise some of the content on this new online resource. Not suprisingly, much of the content is drawn from the GCP Guide and so to that extent there are no great suprises here. However, it is reassuring to see the consistency of responses and to see the questions that the MHRA have chosen to include in this free resource. The questions posed are:
- What is a Trial Master File (TMF)?
- Is a TMF always required?
- Can the sponsor and investigator TMFs be combined?
- Can management of the TMF be subcontracted by the sponsor and what should be considered when using CROs?
- How should the TMF be organised?
- Is it necssary to have SOPs and standard indices for the TMF?
- How should the TMF be stored and who should have access?
- Should the TMF be kept up to date?
- What is regarded as an essential document?
- How should we deal with correspondence, in particular emails?
- Is it acceptable for the TMF to be electronic?
- We scan our documents for inclusion in the TMF. Is this acceptable and can the paper originals be destroyed?
- Will access to the TMF be required during an inspection?
- How long shuld the TMF be retained (archived) after the trial is completed?
- Can the sponsor retain (archive) the investigators TMF?
- Are there any requirements for the archive storage conditions?
- How should electronic documents/data be archived?
- Is there a need for an Archivist?
Are there any suprises in the content? Well, because the content is largely based on the GCP Guide, there were no huge suprises here. However, 2 points did jump out at me. The first was in relation to guidance on management of correspondence and in particular emails. Given the emphasis that the MHRA and other authorities have placed on producing certified copies of documents that are an “exact copy of the original with no loss of metadata”, it is still suprising to see the printing of emails to paper given as an acceptable option. A printout of an email cannot be a lossless copy. Where emails are to be retained electronically, the Outlook pst file format is given as the preferred format despite this not being suitable for long-term retention and being an extremely difficult file format to manage (e.g. searchability, navigation, file size). Portable document format (pdf) is also suggested as a suitable format but not the preferred one; I would question the rationale behind this recommendation and would suggest that PDF/A is the default file format for emails.
Secondly, I liked the structure given in the answer to question 4 (can TMF management be subcontracted). The MHRA have laid out what is effectively a great checklist to be used when studies are contracted out. This should help to avoid an misunderstanding regarding responsibilities for TMF maintenance, which systems are being used, and how documents are to be transferred between parties.
Thanks to the MHRA for another great TMF resource!