MHRA Updates Guidance on Clinical Investigations in Great Britain: Key Implications for Manufacturers

The UK Medicines and Healthcare products Regulatory Agency (MHRA) has published updated guidance on clinical investigations for medical devices in Great Britain, clarifying regulatory expectations under the UK Medical Devices Regulations 2002 (UK MDR) and their interaction with EU requirements.

The guidance, published on 31 March 2026, provides comprehensive direction for manufacturers planning and conducting clinical investigations and highlights several important considerations that may directly impact development strategies, regulatory submissions, and timelines.

Alignment Between Great Britain and EU Frameworks

One of the most notable aspects of the guidance is the continued flexibility for manufacturers to use EU MDR pathways:

• Clinical investigations conducted in Northern Ireland must follow EU MDR/IVDR

• For multi-site studies (GB + NI), a single EU MDR submission to MHRA is sufficient

• Even for GB-only studies, manufacturers may choose to demonstrate compliance with EU MDR instead of UK MDR

What this means for manufacturers:

• Opportunity to streamline regulatory strategy across UK and EU markets

• Potential to avoid duplication of submissions

• Increased importance of aligning documentation with EU MDR standards, even when targeting GB only

When Clinical Investigations Are Required

The MHRA reinforces that clinical investigations are expected in several scenarios, particularly for:

• Implantable and Class III devices

• Devices with novel technologies or materials

• Significant design or performance modifications

• Devices intended for new purposes or indications

• Situations where preclinical testing cannot replicate clinical conditions

Manufacturer impact:

• Early-stage innovation will almost always trigger clinical investigation requirements

• Changes to existing devices may invalidate reliance on legacy clinical data

• Strong justification is required if clinical data is not generated via investigation

60-Day Notification Requirement Remains Critical

Manufacturers must provide a minimum 60-day notice to MHRA before starting a clinical investigation in Great Britain.

Key elements:

• Submission via the IRAS platform

• Investigation may proceed only if no MHRA objection is raised within 60 days

• Research Ethics Committee (REC) approval is mandatory before initiation

Practical implications:

• Regulatory timelines must include both MHRA review and ethics approval

• Delays may occur if documentation is incomplete or inconsistent

• Coordination between regulatory and clinical teams is essential

Clinical Evidence Expectations Are Reinforced

The guidance reiterates that clinical data is central to demonstrating compliance with safety and performance requirements.

Acceptable sources include:

• Scientific literature (with demonstrated equivalence)

• Clinical investigation data

• Combined evidence approaches

However:

• For high-risk devices, clinical investigations are likely unavoidable

• Investigations must confirm:

  • Intended performance under normal conditions

  • Acceptable benefit-risk profile

Key takeaway:
Manufacturers should expect increased scrutiny on clinical evidence quality, especially for innovative or high-risk devices.

Increased Focus on Study Design and Conduct

The MHRA outlines detailed expectations aligned with BS EN ISO 14155:2020 (Good Clinical Practice), including:

• Clearly defined objectives and endpoints

• Adequate sample size and duration

• Robust adverse event reporting

• Full documentation and final reporting

Additional emphasis is placed on:

• Realistic study conditions

• Justification of control groups (or lack thereof)

• Objective and measurable endpoints

Impact for manufacturers:

• Poorly designed studies may lead to regulatory objections or delays

• Alignment with ISO 14155 is no longer optional—it is expected

Post-Market Clinical Follow-Up (PMCF) Expectations

The guidance reinforces that clinical evaluation is not a one-time activity:

• Manufacturers must continuously update clinical evidence

• PMCF is expected, particularly for:

  • Innovative devices

  • High-risk indications

  • Long-term safety concerns

Strategic implication:

• Clinical strategy must extend beyond pre-market approval

• PMCF planning should be integrated early in development

Stricter Oversight on Safety Reporting and Study Changes

Manufacturers are required to:

• Report all serious adverse events to MHRA without delay

• Submit quarterly safety reports

• Notify MHRA of any study modifications before implementation

The MHRA retains the authority to:

• Suspend or terminate investigations

• Withdraw approval if safety concerns arise

What this means:

• Increased operational burden on clinical and regulatory teams

• Need for robust post-submission monitoring systems

• Greater importance of real-time safety data management

Special Scenarios Clarified

The guidance also provides clarity on less straightforward cases:

• Prototype devices: Changes may be allowed within one submission unless risk increases

• Off-label use: May shift regulatory responsibility to clinicians or institutions

• In-house devices: Exemptions apply only under strict conditions

• Humanitarian use: Requires prior MHRA authorization

Manufacturer takeaway:
These scenarios require careful regulatory interpretation and early engagement with MHRA.

Read the full document below.