eTMF Regulations: We are all in the same boat!

This fall showcased two eTMF-related conferences. We recently shared a post covering the key takeaways from these events in detail. Every attendee had a common mission – to continuously learn about how to keep a tidy and effective TMF, and learning tips and tricks from our fellow TMF enthusiasts. We are all part of a constantly growing, evolving, and passionate community, and that was never more palpable than while attending these events and listening to the discussions.

Many interesting topics packed the agendas, but common themes emerged: Nothing is ever black and white, and sometimes we need to make concrete decisions in gray areas not clearly defined in the regulations. In the end, it will be on you – especially if you are the Sponsor.

Do you know who is accountable for the overall TMF deliverable? The Sponsor, even if the CRO is held responsible throughout the trial. That is why it is so important for Sponsors to have clear procedures surrounding TMF oversight, quality, and archiving, and other related processes.

[Regulations No 536/2014 preamble (52)]

During the trial: In order to be able to demonstrate compliance with the protocol and with this Regulation, a clinical trial master file, containing relevant documentation to allow effective supervision (monitoring by the sponsor and inspection by Member States), should be kept by the sponsor and by the investigator. After the trial: The clinical trial master file should be archived appropriately to allow for supervision after the clinical trial had ended.

It is still up to you whether you use a paper-based or an electronic TMF, but it won’t be that way for long. At some point, paper will become obsolete – welcome to the 21st century! Transparency will become more important as regulators begin to more closely follow documentation of ongoing clinical trials. Make sure you update your TMF in a timely and relevant manner to ensure it is available and accessible upon request.

According to Regulation 536/2014, Article 58, TMF documentation needs to be kept for 25 years! Some exceptions may apply depending on your national law. How will these files look in 25 years if they aren’t digital? Inspectors want to be able to reconstruct the entire clinical trial. As one of the inspectors said, they are not there to “find a needle in a haystack”.

[GCP Directive 2005/28/EC: Chapter 4 Article 16]

The trial master file shall provide the basis for the audit by the sponsor's independent author and for the inspection by the competent authority.

During an inspection, TMF owners should ensure that inspectors have read-only access to the entire TMF, and the ability to view and print documents and their audit trails as required.

The million-dollar question still remains: can we destroy all wet ink documents? When do we need certified copies, and how should they be created and/or verified? There is currently no right or wrong answer; it is to be decided by the sponsor.

At TransPerfect Life Sciences Solutions, we help Sponsors and CROs with the process of migrating and archiving TMFs from paper to electronic. We’ll guide you through the whole process and perform scanning, metadata coding, QC, and audit services.

During the conferences we also discussed the number of systems Sponsors should have to maintain. In an ideal world, your systems integrate and talk to each other so your efforts don't have to be duplicated. Our Trial Interactive solution not only integrates with all major systems, but also works in tandem with our other modular solutions that tackle a wide range of systems besides eTMF (SSU, LMS, investigatator portal, and e-feasibility, just to mention just a few).

One of the group challenges at the conference was an exercise in putting together the perfect eTMF. The team that won described a combination of services, support, and product – three mainstays of the Trial Interactive business model.

Following the conference, myself and fellow TMF enthusiasts enjoyed a beautiful evening sailing through Amsterdam’s channels. It was then that it occurred to me that we are all in the same boat: still trying to find the best way to handle TMF in these uncharted waters.