The UK Medicines and Healthcare products Regulatory Agency (MHRA) has updated its guidance on "Clinical trials for medicines: manage your authorisation, report safety issues". These changes, published on 6 February 2025, include major revisions to Development Safety Update Reports (DSURs) and introduce a new user reference guide to streamline submissions.
A (CTA) is the official approval granted by a regulatory authority (such as the UK MHRA) to conduct a clinical trial involving an Investigational Medicinal Product (IMP). It ensures that the trial meets safety, ethical, and scientific standards before it begins.
Why is CTA Important?
Ensures the protection of trial participants.
Confirms that the trial design is scientifically valid.
Verifies that the investigational drug is manufactured to required standards.
Maintains compliance with Good Clinical Practice (GCP) and Good Manufacturing Practice (GMP).
Key Updates in the Guidance
1. Managing Your Clinical Trial Authorisation
Before conducting a clinical trial in the UK, sponsors must obtain MHRA approval. This process varies depending on whether the trial falls under the Combined Review process or the traditional route:
Trials under the Combined Review Process: Applications are submitted through the Integrated Research Application System (IRAS).
Trials under the Traditional Process: Applications are made via the MHRA Submissions portal.
Changes to an authorised trial must follow the appropriate substantial amendment procedures, ensuring compliance with MHRA requirements.
2. Development Safety Update Reports (DSURs) – New Requirements
Online Payment Mandate
From 1 June 2024, sponsors must pay the DSUR submission fee online using the MHRA Pay system before submission.
The payment receipt must be included in the submission; otherwise, the DSUR will be invalid.
Submission Process
Non-Combined Review Trials: Submit via the MHRA Submissions portal, selecting "Development Safety Update Report" as the Regulatory Activity.
Combined Review Trials: Submit via IRAS if any trials in the DSUR were approved under this pathway.
No Duplicate Submissions: Sponsors should avoid submitting DSURs on both platforms to prevent duplicate fees.
DSUR Content Requirements
The DSUR must provide a comprehensive safety analysis of the clinical trial(s), including:
A risk/benefit assessment based on patient safety data.
A line listing of all suspected serious adverse reactions (SARs).
A summary of all SUSARs (Suspected Unexpected Serious Adverse Reactions) across the trial.
Additional region-specific safety information.
Compliance with ICH E2F guidelines.
Annual Safety Report Alternatives
For low-risk trials, a Health Research Authority (HRA) Annual Progress Report may replace the DSUR.
Sponsors must clarify this in the cover letter with the appropriate trial identifiers.
3. Serious Breaches & Urgent Safety Measures
Reporting Serious Breaches
Sponsors must report any serious breaches of Good Clinical Practice (GCP) or protocol that could affect patient safety or data integrity.
Reports must be submitted within seven days of becoming aware of the breach.
Implementing Urgent Safety Measures
If an immediate safety risk arises, sponsors may modify the trial without prior MHRA approval but must notify the agency within three days.
4. SUSAR & Safety Reporting for Investigational Medicinal Products (IMPs)
Sponsors must report all UK-based SUSARs to the MHRA via the ICSR Submissions Portal.
Fatal and life-threatening SUSARs must be reported within seven days, while others must be reported within 15 days.
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