Applying for Clinical Trial Approval for Medicines in the UK

Overview

This guidance outlines the process for applying for clinical trial authorisation (CTA) for clinical trials of investigational medicinal products (CTIMPs) in the UK. It covers eligibility, application processes, fees, timelines, and post-authorisation management. Applies to trials meeting the clinical trial definition under Regulation 2 of the Clinical Trials Regulations. Source: https://www.gov.uk/guidance/clinical-trials-for-medicines-apply-for-approval-in-the-uk

Clinical Trial Definition

A clinical trial is any investigation in human participants (other than non-interventional) intended to discover or verify clinical, pharmacological, or pharmacodynamic effects of medicinal products, identify adverse reactions, or study absorption, distribution, metabolism, and excretion, with the object of ascertaining safety or efficacy. If it meets the definition, it requires CTA. Use the algorithm or IMP/non-IMP guidance to confirm. Mock examples provided. Source: https://www.gov.uk/guidance/clinical-trials-for-medicines-apply-for-approval-in-the-uk

What This Guidance Does Not Cover

Medical devices: See separate guidance. Borderlines: Check if the product is a medicine. Source: https://www.gov.uk/guidance/clinical-trials-for-medicines-apply-for-approval-in-the-uk

Trial Sponsor and Legal Representative

Sponsor: Person/institution responsible for initiation, management, and financing. Can be joint. Must be established in the UK or an approved country (e.g., EU/EEA). If not, needs a legal representative in an approved country. Source: https://www.gov.uk/guidance/clinical-trials-for-medicines-apply-for-approval-in-the-uk

Registration of Clinical Trial

From 1 Jan 2022, HRA auto-registers CTIMPs via ISRCTN. Still require public registration on a database (e.g., ISRCTN, ClinicalTrials.gov). Defer for adult Phase I. Include registry number in IRAS; if unavailable, email MHRA within 6 weeks of first participant. Source: https://www.gov.uk/guidance/clinical-trials-for-medicines-apply-for-approval-in-the-uk

Combined Review Process

From 1 Jan 2022, all new CTIMPs via combined review: Single application/route, co-ordinated MHRA + ethics committee review. Submit via new IRAS. For IMP + Device: See specific guidance. Source: https://www.gov.uk/guidance/clinical-trials-for-medicines-apply-for-approval-in-the-uk

In Vitro Diagnostic (IVD) Devices Including Companion Diagnostics

Identify in covering letter/protocol if IVD/companion diagnostic used. IVD definition provided. Companion: Essential for safe/effective use of corresponding medicinal product.

For CTIMPs in GB:

• Must bear UKCA/CE mark or health institution exemption.
• If no mark/exemption: Conduct analytical performance study or submit Tabular Summary + checklist. Requirements detailed with flow diagram. Response to queries: 14 days. Register if determining clinical performance. For NI: Separate guidance. Source: https://www.gov.uk/guidance/clinical-trials-for-medicines-apply-for-approval-in-the-uk

Documents to Submit

Via IRAS. Specific MHRA docs:

• Covering letter: State Phase I healthy volunteer for shortened assessment; highlight PO number; confirm CE marking if IVD.
• IMPD: Not ASMF.
• Manufacturer’s authorisation + GMP for non-EU sites.
• IMP labelling content; justify absence. All docs: Copy-paste functional, no passwords. IMPD examples provided. Source: https://www.gov.uk/guidance/clinical-trials-for-medicines-apply-for-approval-in-the-uk

Assessment and Timelines

Initial assessment: 30 days. Healthy volunteer/Phase I non-oncology: Shortened if eligible. Outcomes: Acceptance, conditional, or non-acceptance. Response to non-acceptance: Usually 14 days. Final decision: Usually 60 days; 90 days for gene/somatic cell/ATMP/GMO. Expert advice for high-risk. Common issues guidance. Withdraw before non-acceptance. Source: https://www.gov.uk/guidance/clinical-trials-for-medicines-apply-for-approval-in-the-uk

New Notification Scheme

Streamlined for low-risk Phase 4/certain Phase 3: 14-day processing. Not for Phase 1/2/FIH/amendments. Criteria detailed. Register interest via form. Submit via IRAS; full docs required. Acceptance: 14 days; objection if ineligible, then full review. Source: https://www.gov.uk/guidance/clinical-trials-for-medicines-apply-for-approval-in-the-uk

Complex innovative designs: Justify in app; major adaptations via amendments. Dialogue with MHRA. Consensus paper. ATMP-pretreated patients points to consider. Source: https://www.gov.uk/guidance/clinical-trials-for-medicines-apply-for-approval-in-the-uk

Fees

Based on trial type. Apply to Notification Scheme. Invoice post-submission; pay on receipt. Contact details. PO in covering letter. Source: https://www.gov.uk/guidance/clinical-trials-for-medicines-apply-for-approval-in-the-uk

Post-Authorisation Management

Report safety issues per guidance. Amendments: Substantial for major changes. Annual Safety Reports: Fee applies. Contact for queries. Email for comms. Source: https://www.gov.uk/guidance/clinical-trials-for-medicines-apply-for-approval-in-the-uk

Updates

Last on 18 Feb 2026 (clarified definition); see history for changes (e.g., IVD updates 22 Aug 2025). Source: https://www.gov.uk/guidance/clinical-trials-for-medicines-apply-for-approval-in-the-uk