The previous system, based on the EU Clinical Trials Directive, was widely seen as overly bureaucratic, slow, and difficult to navigate - particularly in response to emerging health threats and the pace of modern innovation.
With this in mind, the new legislation aims to:
COVID 19 had already demonstrated to many clinical trial teams that they needed to shift towards paperless systems.
The new regulation actively supports and encourages a shift towards digital systems - particularly for the management of the Trial Master File (TMF).
While reducing complexity in approvals, it formalises digital compliance requirements through the adoption of the Good Clinical Practice guidelines ICH GCP E6 (R3).
It also introduces new requirements for transparency and data publication, which will make paper-based compliance considerably more onerous.
For those new to managing digital compliance with the MHRA, there may be additional document control complexities to consider that outstrip what’s possible with SharePoint, Dropbox or Google Drive.
New legislation now requires all Trial Master File (TMF) records to be retained for at least 25 years after a trial ends. This marks a major shift - from managing physical storage to ensuring the long-term preservation of digital data.
To meet this challenge, CTUs must establish a validated digital archive, separate from the primary eTMF system. This archive should include clear procedures for periodic data migration and file format conversion, ensuring documents remain accessible and readable over time.
If you’re looking for eTMF software - ensure that your data is going to be accessible and retrievable in a format you can archive on your own systems.
Some quality management software used for eTMF construction may require you to upload documentation to their systems in ways that make them difficult to download and store elsewhere in future.
Don’t get locked into a system that makes future archiving more difficult!
The new ICH GCP E6 (R3) formalises standards for data governance and system security.
This includes demonstrating that the eTMF maintains data integrity (in line with ALCOA+ principles), and that it records complete audit trails using UTC timestamps with approvals managed by Annex 11 compliant eSignatures.
There is also a responsibility for Computerised Systems Validation (CSV) to prove their systems are fit for purpose.
If you’re going it alone by building your eTMF in SharePoint or adopting a third party eTMF solution - you should carefully consider the kind of documentation and resource you’ll need to manage this CSV process.
The revised GCP encourages CTUs to focus resources on what matters most - areas critical to quality (CtQ).
The eTMF should integrate with the trial’s Quality by Design (QbD) framework to support this.
Instead of manually reviewing every document, quality teams can use real-time TMF data to carry out targeted, risk-based reviews, focusing effort where it will have the biggest impact.
GCP requirements for digital compliance will mean re-working process and quality documentation for your eTMF.
Existing paper-based SOPs will no longer apply. CTUs must develop new digital SOPs that cover:
These SOPs must be rolled out across all research staff to ensure consistent, compliant operations.
Under the updated law, CTUs must register trials and publish lay summaries of results within 12 months of trial completion.
To stay compliant, CTUs must build workflows into the eTMF to track these deadlines, ensuring timely filing, quality checks, and publication — reducing the risk of fines or audit findings.
For those adopting a new eTMF system ensure that it is flexible enough to help you manage these kind of publication timetables.
The UK’s new clinical trials legislation reflects and supports the inevitable shift towards digital-first trial management. It provides clear guidelines for digitising your eTMF while ensuring the absolute integrity of documentation and data.
For CTUs, this is both a challenge and an opportunity.
From long-term digital archiving and system validation to transparency, oversight, document controlt, the new framework sets a clear expectation: trial documentation must be secure, accessible, and auditable for decades to come. That means rethinking legacy processes, retraining staff, and investing in systems that are built for compliance from the ground up.
Now is the time for CTUs to move beyond minimum requirements and build digital infrastructure that not only meets regulatory standards but also supports faster, more flexible trial delivery. Those who adapt early will be best placed to lead in a more agile, globally competitive UK research environment.