UK MHRA Guidance: Clinical Trials in the UK: Quality, Risk Proportionality, GMP, and Radiopharmaceutical IMPs
- Sharan Murugan
- Mar 29
- 2 min read
The UK regulatory landscape for clinical trials is undergoing a significant transformation with the implementation of updated Medicines for Human Use (Clinical Trials) Regulations, effective from 28 April 2026. These changes emphasize quality by design, risk-based approaches, and strengthened manufacturing standards, ensuring both participant safety and data integrity.
Scope
This guidance applies to all UK clinical trials involving investigational medicinal products (IMPs). It aligns with ICH E8 (R1), which provides scientific principles, and ICH E6 (R3), which outlines operational Good Clinical Practice (GCP). Together, they support proper design, conduct, and reporting of trials.
Sponsors, investigators, and delegated parties are required to follow all relevant guidance under UK Clinical Trials Regulations.
Core Concepts
Quality by Design (QbD) ensures that quality is built into the trial from the beginning rather than checked later.
Risk-Based Quality Management (RBQM) introduces a structured approach to identify, assess, and control risks affecting participant safety and data reliability.
Risk proportionality ensures that oversight and processes are aligned with the level of risk, considering study complexity, participant safety, and importance of data. This avoids unnecessary burden while maintaining compliance.
MHRA Expectations
The MHRA expects organisations to apply QbD and RBQM throughout the trial lifecycle, focusing on critical-to-quality factors and proportionate monitoring.
Compliance with ICH GCP principles, embedded in UK law, is essential to ensure both efficiency and participant protection.
Essential Records
Essential records must be maintained to demonstrate trial conduct and compliance. These records should enable reconstruction and evaluation of the trial and support regulatory inspections, ensuring transparency and data integrity.
Regulatory Framework
This guidance supports the amended UK Clinical Trials Regulations (2025), applicable from April 2026.
Sponsors, investigators, manufacturers, and service providers must comply with all relevant guidance to ensure proper handling and manufacturing of investigational medicinal products.
Good Manufacturing Practice (GMP)
GMP defines the principles governing the manufacture of IMPs. In Great Britain, it follows Commission Directive 2003/94/EC, and in Northern Ireland, Commission Delegated Regulation 2017/1569.
These frameworks ensure that products are consistently produced and controlled to quality standards. The UK remains aligned with international GMP systems such as PIC/S and EU frameworks.
Labelling Requirements
Updated regulations require the use of unique identification codes to ensure traceability of IMPs.
Labelling must align with quality systems, including controlled printing and artwork management, to maintain consistency and accuracy.
Radiopharmaceutical IMPs
Radiopharmaceutical products are medicinal products containing radionuclides used for diagnostic or therapeutic purposes.
The updated guidance introduces specific provisions to address their unique characteristics and regulatory needs.
Manufacturing and Control
Diagnostic radiopharmaceutical IMPs can be manufactured at licensed UK facilities, and in certain cases under alternative licensing arrangements.
The guidance outlines how these products should be prepared, handled, and used in clinical trials, balancing flexibility with safety and control.
Radiolabelling
Radiolabelling involves adding radioactive components to investigational products.
This includes:
Radiolabelling of diagnostic ‘cold kits’
Full manufacture with radioactive components
Specific labelling requirements for diagnostic products
Stricter controls for therapeutic radiopharmaceutical IMPs due to higher risk
References
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