As part of the shift towards a risk-proportionate regulatory framework, the MHRA’s Clinical Trials Unit ran a Route B substantial modifications pilot from 1 October 2025 to 31 March 2026 to test a new process to streamline the review of modifications to low-risk approved clinical trials.
Any modification that will be eligible under section 11B of the Medicines for Human Use (Clinical Trials) (Amendment) Regulations 2024 were eligible to join the pilot.
The benefits
The aim is to cut the time it takes us to review applications from 35 to 14 days by reducing regulatory hurdles for sponsors of low-risk trials and enabling expert assessors to focus on higher-risk trials.
This will lead to faster initiation of low-risk trials - reducing administrative blocks without compromising participants’ safety.
The results
By the end of March, we had received:
- 94 registrations. A healthy mix across sectors (53% commercial sponsors and 47% non-commercial sponsors).
- 26 applications submitted across industry and academia.
The average end-to-end processing time was 7 days, well below the 14-day threshold, and significantly shorter than a standard substantial amendment.
The scheme has attracted positive feedback from the research community. Several major global pharmaceutical companies submitted multiple applications through the pilot.
Next steps
The groundwork has now been laid for this pathway to become legally mandated when the new Clinical Trials Regulations are implemented on 28 April 2026.
As well as supporting trial sponsors in preparing for the regulatory reforms, the pilot provided an opportunity to identify any challenges and finetune our internal processes ahead of the formal launch.
Based on sponsors’ feedback, we’ve amended the application process, tweaked the form and simplified the guidance. We are now ready for the full implementation of Route B Substantial Modifications at the end of April.
Please subscribe to our guidance page Clinical trials for medicines: modifying a clinical trial approval for the latest information and updates to the Route B process.
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