UK MHRA Guidance: Applying for Clinical Trial Authorisation (CTA)

On 22 August 2025, the Medicines and Healthcare products Regulatory Agency (MHRA) published an updated version of its guidance “Clinical trials for medicines: apply for authorisation in the UK.” Originally issued in December 2014, this guidance has been periodically revised to reflect evolving regulatory frameworks, including the impact of Brexit, COVID-19, and the UK’s shift towards a risk-proportionate and streamlined approval process.

This comprehensive guidance outlines the requirements, processes, and expectations for sponsors, investigators, and companies wishing to conduct clinical trials of investigational medicinal products (CTIMPs) in the UK.

When a Clinical Trial Authorisation (CTA) is Needed

A CTA is mandatory if the clinical study involves an investigational medicinal product (IMP). Situations requiring a CTA include:

• First-in-human studies.

• Trials testing a new indication, formulation, or route of administration.

• Comparative studies against existing therapies.

MHRA clarifies exemptions for non-interventional studies, where medicines are used within their licensed indications without altering prescribing practice. The MHRA acknowledges lessons learned during the pandemic, particularly the need for flexibility and efficiency in clinical trial oversight.

Every trial must have a sponsor (company, institution, or individual) responsible for initiation, management, and financing. For non-UK sponsors, a UK-based legal representative must be appointed to ensure regulatory accountability.

Combined Review of Investigational Medicinal Products (CTIMPs) CTIMPs must be registered in a publicly accessible database (such as ISRCTN or ClinicalTrials.gov) before enrolment of the first participant. This aligns with WHO and EU/UK commitments to trial data transparency. MHRA has introduced a Combined Review Service (formerly known as Combined Ways of Working, or CWoW).

This allows sponsors to submit a single application covering:

• Clinical trial authorisation (MHRA review)

• Research ethics committee (REC) approval

This parallel review reduces timelines and increases efficiency. The scope also includes combined reviews of CTIMPs and medical devices, and trials involving companion diagnostic in vitro diagnostic (IVD) devices.

Applications must include:

• Model IMPDs (Investigational Medicinal Product Dossiers): Detailed information on product quality, safety, and manufacture.

• Investigator’s Brochure (IB): Safety and efficacy information for trial investigators.

• Trial Protocol and Case Report Forms (CRFs).

• Participant Information Leaflet and Consent Forms.

MHRA provides templates and model IMPDs to guide applicants.

Assessment of Submissions

• Initial combined assessment is usually within 30 days (14 days for some lower-risk notification scheme trials).

• Possible outcomes: full approval, conditional approval, grounds for non-acceptance (with opportunity to respond).

• Genetic therapies and ATMPs may have longer (up to 90 days) decision timelines.

• Withdrawal is possible at any point before a final decision or non-acceptance letter is issued.

• Amendments to approved CTAs must be submitted and authorised before implementation, especially for substantial amendments (e.g., dosage changes, protocol updates).

This guidance is essential reading for sponsors, CROs, and academic researchers involved in UK-based clinical trials.

For full details and templates, refer to the official MHRA page:👉 Clinical trials for medicines: apply for authorisation in the UK