One of the questions that I get asked repeatedly is what exactly is the trial master file (TMF). I represented this graphically a number of years ago, as follows:
For quite a while, industry thought that the TMF was just those documents listed in Section 8 of ICH GCP. However, many regulatory agencies – most recently the MHRA in their GCP Guide – have made it clear that the TMF is much wider in scope than this. The documents listed in Section 8 of ICH GCP are just a minimum list of essential documents. The TMF should also contain other trial-related records that “permit evaluation of the conduct of the trial and the quality of the data produced”. Industry can get assistance in determining what this constitutes by referring to the TMF Reference Model. There are also some supporting files that are generally considered to be outside the scope of the TMF but it should be noted that these files are still potentially subject to inspection. Examples include SOPs, training records and computer system validation files.
So what then is an eTMF and is this the same as an eTMF system? The answer depends on the scope of content that you intend adding to your electronic document management system. Whilst some regulatory agencies have indicated that their preference is to have a single system that holds the whole content of the TMF, this view is not held by all agencies. Therefore, it is permissible for your TMF to be managed in more than one electronic system and in more than one paper system, or even a hybrid of both (i.e. some in paper and some in electronic). There does seems to be a trend towards having a single system but the critical issue is that your SOPs must define which system(s) (paper and electronic) the TMF content is held in. It is also advisable to avoid having content duplicated in paper and electronic format. In other words, if you have invested in an eTMF system to manage some or all of the TMF content, ensure your SOPs define this as the official repository for that content and any hard-copies as temporary convenience copies only (though best to avoid hard-copy as much as possible!). This will take away any obligation to do reconcilliation and QC between hard-copy and electronic. Where team members need hard-copy to do their job, I’d advise generating these convenience copies from the official electronic source, bearing an appropriate watermark that identifies the source.