UK MHRA Updates Guidance: GCP Inspections and Clinical Investigations for Medical Devices
The Medicines and Healthcare products Regulatory Agency (MHRA) has updated two guidance documents covering Good Clinical Practice (GCP) inspections for medicinal product clinical trials and clinical investigations for medical devices.
Both guidance documents were updated on 6 November 2026, providing information on regulatory compliance, inspection procedures, application requirements and clinical investigation responsibilities.
GCP Compliance and Inspection Programme
The MHRA's guidance outlines GCP inspection requirements for organisations involved in clinical trials of medicines, including pharmaceutical companies, Contract Research Organisations (CROs), universities, NHS hospitals, laboratories and clinical research organisations.
Based on ICH E6 (R3) Good Clinical Practice, the guidance covers the design, conduct, analysis and reporting of clinical trials. Sponsors must notify the MHRA of serious breaches of GCP or clinical trial protocols.
The MHRA conducts routine risk-based inspections and triggered inspections to evaluate compliance. Risk-based inspections may be systems-based, examining organisational procedures and quality systems, or trial-specific, focusing on individual clinical trials.
Triggered inspections may arise from serious breach notifications, whistleblowers, regulatory intelligence or information received from other organisations, including the Health Research Authority (HRA).
Pre-Inspection Requirements and Trial Master File
Organisations selected for inspection must provide a GCP inspection dossier and clinical trial spreadsheet within 30 days of receiving the request. The MHRA has also introduced specific documentation templates for organisations providing computerised systems supporting clinical trials.
The Trial Master File (TMF) must be complete and accessible to inspectors, including electronic records and emails. Where multiple electronic systems are used, direct access must be provided. Sponsors must also ensure access to relevant records maintained by subcontracted service providers.
Inspection Findings and CAPA
MHRA inspections involve document reviews, interviews with relevant personnel and examination of clinical trial activities. Inspection findings are classified into three categories:
Critical: Significant non-compliance that jeopardises participant safety, affects data reliability or indicates systematic quality failures.
Major: Significant regulatory departures that could develop into critical issues if not addressed.
Other: Findings that do not meet the critical or major classification.
Following inspection, organisations must submit a Corrective and Preventive Action (CAPA) plan and, where required, an impact assessment. Once adequate responses are received, the MHRA issues a GCP inspection statement.
Critical findings are referred to the GCP Inspection Action Group (IAG2), which may consider additional actions, including early re-inspection, periodic reporting, suspension of Clinical Trial Authorisations (CTAs), infringement notices or prosecution.
Sponsor Responsibilities and Regulatory Oversight
The guidance reinforces that sponsors remain responsible for GCP compliance across their clinical trials, including activities performed by contractors and subcontractors. Appropriate monitoring, contractual arrangements and oversight mechanisms are important for maintaining compliance.
The guidance also covers inspection fees, inspection metrics, infringement notices and access to electronic health records by sponsor representatives.
Clinical Investigation Notification and Application Requirements
The MHRA guidance explains how manufacturers and sponsors should notify the agency before conducting clinical investigations involving medical devices.
Where an investigation requires an MHRA application, sponsors must notify the agency at least 60 days before starting the investigation. Certain devices already UKCA, CE or CE UKNI marked for the intended purpose under investigation do not require a separate notification.
Applications for Great Britain and Northern Ireland must follow the respective regulatory requirements. Certain in-house medical devices manufactured by healthcare establishments for their own patients may also qualify for exemptions.
Application Submission, Fees and SME Support
Clinical investigation applications must be submitted electronically through the Integrated Research Application System (IRAS), together with the applicable documentation and fees.
The MHRA provides payment easements for eligible small and medium-sized enterprises (SMEs), allowing 50% of the fee to be paid following application validation, with the remaining amount payable within six months of the first invoice.
The guidance also introduces a clinical investigation fee waiver programme for eligible UK micro and small enterprises developing innovative medical devices.
The programme runs from 20 April 2026 to 5 April 2027, or until all available waivers are granted. Ten fee waivers are available for eligible Class I, IIa, IIb and Class III devices, excluding active implantable devices.
Eligible applicants must demonstrate that their device is new or represents a novel modification, addresses an unmet clinical need without an equivalent UK-approved solution, and has potential to benefit patients or the health and social care system.
Assessment and Regulatory Decision
For applications in Great Britain, the MHRA confirms within five working days whether the application is valid and whether the 60-day assessment period has started.
The assessment evaluates device safety, performance and the proposed clinical investigation design. The MHRA may request additional information or arrange discussions where potential grounds for objection are identified.
A final decision, either an objection or no-objection letter, is issued by the 60th day.
Parallel Review for Combined Studies
Clinical studies involving both a Clinical Trial of an Investigational Medicinal Product (CTIMP) and a medical device clinical investigation must be submitted through the MHRA's Parallel Review pathway, previously known as the combined IMP+Device pathway.
This approach addresses the separate regulatory requirements and assessment timelines applicable to medicinal products and medical devices, with the longer-term objective of streamlining the submission process.
Amendments and Safety Reporting
Following receipt of a no-objection letter, sponsors must notify the MHRA of proposed amendments and obtain a further no-objection letter before implementing changes.
The notification should include a covering letter, a summary and justification of proposed changes, clean and red-lined versions of amended documents, and a signed statement addressing the potential impact on patient, user and third-party safety.
Sponsors must also fulfil ongoing reporting responsibilities, including:
Reporting serious adverse events through the MHRA MORE portal.
Submitting quarterly summary reports (QSRs) on the overall safety profile.
Reporting clinical investigation deviations at UK sites.
Notifying the MHRA of temporary halts or early termination.
Submitting end-of-study reports.
Northern Ireland Requirements
Clinical investigations involving Northern Ireland must comply with the EU Medical Device Regulation (EU MDR 2017/745). A single MHRA application can cover the relevant Northern Ireland and Great Britain sites within the same investigation.
For Northern Ireland applications, the MHRA confirms application validity and commencement of assessment within 10 calendar days after receiving the submitted documents. Substantial modifications require prior MHRA authorisation before implementation.
The guidance also addresses HRA and Health and Care Research Wales (HCRW) approval requirements and other clinical investigation procedures.
Comments