UK's Substantial Modifications Pilot for Clinical Trials

The new UK clinical trials regulations were approved by Parliament in April 2025 and will come into effect on 28 April 2026. Once implemented, substantial modifications that meet the pre-defined criteria will be eligible for the automatic approval process. This will speed up the modification process, providing the applicants with a decision from the MHRA within 14 days from validation.

Modifying a Clinical Trial Approval

Sponsors are responsible for assessing, whether a modification is substantial, minor or a modification of an important detail, using a risk-based approach. For substantial modifications, the sponsor must then determine whether it is a Route A or a Route B substantial modification. If the change meets the definition of a Route B substantial modification, it is eligible for automatic MHRA approval. The justification for this decision should be clearly documented. A modification is considered a Route B substantial modification based solely on the nature of the modification itself, regardless of whether the clinical trial was authorised via automatic authorisation.

Where a Route B substantial modification involves a change to any quality documentation (i.e. the IMP dossier, the Good Manufacturing Practice (GMP) documentation or the labelling documents), applicants should make this clear in the cover letter. The MHRA will use this information to determine whether to undertake a full review of the modification before issuing a decision.

The Route B substantial modification pilot runs from 1 October 2025 to 31 March 2026. From 28 April 2026, the Route B process will be mandatory for all eligible modifications to a clinical trial.

Further information can be found on the MHRA Inspectorate Blog.