Inspection readiness of electronic TMF

We are using eTMF (electronic Trial Master File) more and more in clinical trials, but the sponsor eTMFs are not always met the requirements by the inspectors, which resulted several recent inspection findings.

Here are 7 recommendations for how to ensure inspection readiness of eTMF.

Prior to an inspection, the inspector will usually discuss with the sponsor and investigator(s) the logistics of making the TMF available to the inspectors. The sponsor should ensure following:

1. Immediate access to e-TMFs ( live and those archived on servers), i.e. the only delay would be the time needed to set up inspector access to the requested trials.
2. Unrestricted direct read-only access to the TMF, so that inspectors are reviewing the same TMF as is being used by the staff conducting the trial.
3. Direct access includes all the systems that comprise the TMF as defined by the sponsor. However, it is accepted that for certain systems it may be necessary for direct access to be assisted by a representative of the sponsor.
4. The inspectors have rights to seize original trial documentation if circumstances arise that require it. The inspectors can always request copies or print outs and can retain some or all of these.
5. The inspectors expect that an e-TMF should adequately replicate the paper based system that it is replacing and provide for suitable document identification, search, prompt retrieval and marking for future reference/copying.
6. The e-TMF should allow review in an efficient manner, analogous to that possible with paper TMFs. Such a review should not take longer to be undertaken than for a paper TMF and should allow efficient, straightforward navigation and opening of documents permitting searching and browsing (analogous to leafing through a paper file). This would include:

• a folder structure to allow easy identification of TMF sections;
• a folder/file naming convention that readily identifies what each file/document is, so inspectors/auditors do not have to open numerous documents to locate those they need;
• the ability to open more than one document at a time to allow comparison (so size of screens or double screens important);
• the ability to provide access to the same type of document across all studies/sponsors/product etc. (i.e. if inspector needs to review documents for all/some selected studies/sites);

7.  The system is recommended to have an efficient speed of access and ideally not require the use of a nomenclature document or require time spent opening non self-evident named files to determine  their content.

It is acknowledged that inspectors may need to familiarise themselves with an e-TMF. Any training  should be an option for the inspector to choose and is anticipated to be very brief (taking no more than  an hour).

The e-TMF will need the use of suitable equipment, to be provided by the sponsor, for the inspector to view the documents. This equipment is recommended to facilitate the presentation of the documents at actual size.

Reference:  EMA Guideline on GCP compliance in relation to trial master file (paper and/or electronic) for content, management, archiving, audit and inspection of clinical trials, 2017

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