MHRA Issues Updated Guidance on Submitting Clinical Investigation Proposals

On 31 March 2026, the UK Medicines and Healthcare products Regulatory Agency (MHRA) published updated guidance detailing the requirements for submitting clinical investigation proposals for assessment.

The guidance applies to all clinical investigations conducted in the UK and provides clarification on regulatory pathways, submission processes, and required documentation.

Regulatory Framework Depends on Study Location

The guidance confirms that different regulatory frameworks apply depending on where the investigation is conducted:

• Great Britain (England, Wales, Scotland):
  Governed by the UK Medical Devices Regulations 2002 (UK MDR 2002)

• Northern Ireland:
  Continues to follow EU MDR (2017/745) and IVDR (2017/746)

• Studies involving both Great Britain and Northern Ireland:
  Must be submitted under EU MDR requirements, with a single MHRA application covering all sites

This distinction is explicitly outlined and remains a key consideration for manufacturers planning UK clinical investigations.

Submission via IRAS and Validation Timelines

All applications must be submitted through the Integrated Research Application System (IRAS).

The guidance specifies validation and assessment timelines:

• Great Britain:

  • Validation within 5 working days

  • 60-day assessment period starts after a valid application is confirmed

• Northern Ireland (EU MDR pathway):

  • Validation confirmation within 10 calendar days

  • If issues are identified, a 10-day response period is provided before validation

The MHRA notes that the assessment period only begins once a valid application has been confirmed.

Emphasis on Complete and High-Quality Submissions

The MHRA highlights that a common reason for objection is the failure to provide all required data within statutory timelines.

Manufacturers are expected to ensure that:

• The device has been manufactured and tested for safety and performance prior to submission

• The submission includes sufficient evidence to demonstrate compliance with:

  • Essential Requirements (UK MDR), or

  • General Safety and Performance Requirements (EU MDR)

Detailed Documentation Requirements

The guidance provides a comprehensive list of required documents, including:

• Clinical Investigation Plan (in line with ISO 14155:2020)

• Investigator’s Brochure

• Risk Analysis (aligned with ISO 14971:2019)

• Device description and technical documentation

• Bench and pre-clinical testing summaries

• Clinical experience data (if available)

• Instructions for Use and labelling

• Checklist for Essential Requirements or GSPR

Additional documentation may be required depending on the device, including:

• Software documentation

• Biological safety assessments (ISO 10993 series)

• Sterilisation validation reports

The guidance also specifies expectations for:

• Study design and justification (including sample size)

• Statistical methods and endpoints

• Adverse event reporting procedures, referencing MEDDEV 2.7/3 and MDCG 2020-10/1

Key Considerations for Manufacturers

Based on the guidance, manufacturers should take into account:

• Regulatory pathway selection:
  The applicable framework (UK MDR vs EU MDR) depends on study location

• Submission readiness:
  Applications must be complete and supported by appropriate technical and clinical evidence

• Documentation scope:
  A broad set of technical, clinical, and risk management documents is required

• Validation dependency:
  The assessment timeline will not start until the application is considered valid

MHRA Encourages Pre-Submission Interaction

The MHRA indicates that manufacturers may contact the agency with questions prior to submission and, where appropriate, request a pre-submission meeting.

Final Note

This guidance provides a detailed framework for preparing and submitting clinical investigation applications in the UK, with clear expectations on documentation, validation, and regulatory alignment.

Manufacturers planning clinical investigations should ensure that all required evidence and documentation are in place prior to submission to avoid delays during validation and assessment.

Read the full document below.