e-TMFs can be acceptable to regulatory authorities if they meet the requirements for TMFs that are
described in Directive 2005/28/EC and the related guidance in volume 10 of the rules governing
medicinal products in the European Union. For the purposes of GCP inspection (and audit), the following
attributes apply:
• The e-TMF should allow review in an efficient manner, analagous to that possible with paper TMFs. Such a review should not take longer to access than for a paper TMF. (Efficient, straightforward navigation and opening of documents permitting searching and browsing (analogous to leafing through a paper file).
• Inspectors/auditors should have direct access to the e-TMF and the documents held in the e-TMF (the live system, not a copy) to allow direct searching.
• Documents held on an e-TMF should be evidently authentic, complete and legible copies of the
original documents.
• The e-TMF system should have validated methods for preventing any changes being made to the TMF documents, this includes the process of transferring from original media to the electronic medium.
• The process for transferring original TMF documents to e-TMF (or other media) should be robust and have been validated to prevent failure of transfer the entire content of the original TMF without loss ( i.e. there should be a demonstrable 1:1 mapping between the content of the original TMF and the e-TMF ).
Additional considerations
Documents on e-TMF should remain complete and legible in all aspects giving information about the way
the document was prepared. This holds especially for contracts and forms completed by hand. Transfer to
e-TMF should not (be used to) conceal any physical change to the document such as physical cut & paste
to remove or add items, use of correction fluid etc.
It is helpful if the e-TMF has:
• 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).
Future considerations
For the future, it would help if e-TMFs were available through secure internet links. This would help to
avoid some unnecessary travel when accessing the TMF. This approach has advantages over supplying
e-TMFs by e-mail, DVD etc., in that only one version of the e-TMF needs to exist, which can be continually
updated for ongoing trials.
Advantages
• Assisting the development of virtual inspections.
• Improving the efficiency of the inspection process (and lowering the carbon footprint of trial management, inspection and audit).
