Regulatory Framework after Brexit
The revised guidance reorganizes the relationship between the UK MDR 2002 framework and the differing regulatory regimes of Great Britain (GB) and Northern Ireland (NI). GB investigations follow UK MDR requirements, while NI studies must fully comply with EU MDR. The document presents practical “dual-track” case examples, advising sponsors on how to plan documentation to satisfy both routes and avoid duplication of submissions.
IRAS Submissions and Documentation Requirements
MHRA has expanded IRAS submission content expectations, including an enhanced protocol synopsis, detailed clinical justification, risk analysis, data management strategy, and monitoring plan. Clear guidance is provided for participant materials (including digital consent forms), interoperability of eConsent systems, and transparency of decentralized trial processes. Early scientific consultations are encouraged for complex studies involving Class IIb and III devices.
Role of Sponsor, UKRP, and Supply Chain
Sponsors outside the UK must appoint a UK Responsible Person (UKRP) accountable for local compliance, device importation, labeling, and communication with MHRA and Research Ethics Committees (REC). The updated guidance stresses the need for explicit contractual allocation of responsibilities across sponsors, CROs, and technology vendors, including service-level agreements covering cybersecurity and incident notification obligations.
Ethics, Safety, and Reporting
The updated document introduces greater ethical and safety rigor. It clarifies SAE/SADE definitions and timelines, establishes harmonized templates for event reporting, and mandates procedures for study suspension or urgent safety measures. Ethical provisions focus on participant equality, proportionality of remote interactions, and accessibility within decentralized trials. MHRA also emphasizes consistency between clinical investigation safety reporting and post-market surveillance for CE/UKCA-marked devices.
Monitoring and Quality Management
The guidance fully embraces risk-based monitoring principles. Monitoring plans must logically link risk identification to chosen oversight mechanisms (centralized, remote, or on-site) and define action thresholds. Independent QA audits and measurable CAPA closure are required. MHRA recommends “quality by design” approaches where risk assessment drives study design and data collection strategy.
GB vs NI Differences and Multi-Site Studies
Matrix tables outline regulatory divergences in notification, labeling, and specimen handling between GB and NI. Sponsors running multi-country studies are advised to build buffer timelines to accommodate dual REC/MHRA review and synchronize protocol versions across regions.
Archiving, Transparency, and Inspection Readiness
The guidance mandates at least 10 years of document retention and continuous inspection readiness. Sponsors should maintain complete eTMF structures, consistent audit trails, and retrievable decision logs. MHRA encourages mock inspections and internal readiness assessments, especially for decentralized and hybrid studies where digital systems play a critical role.
Implications for Manufacturers and Sponsors
In practical terms, sponsors should recalibrate IRAS workflows, update UKRP and vendor agreements, review DCT-related risk frameworks, and align RBM strategies with MHRA expectations. Consistency with ISO 14155 remains the foundation of clinical quality, while thorough documentation and traceability continue to be the most effective safeguards during inspections and conformity assessments.