General Practices (GPs) are increasingly becoming valuable research sites for clinical trials, offering access to appropriate and diverse patient populations needed for clinical trial. However, for GP sites to operate successfully in clinical research, they must navigate complex regulatory landscapes, particularly those governed by the United States Food and Drug Administration (FDA), the European Medicines Agency (EMA), and the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) depending on the GP practice geographical location.
Side note: The European Medicines Agency is not applicable to the UK as a whole as of 1 January 2021 as a result of Brexit; however, EU pharmaceutical law continues to apply to Northern Ireland, as outlined in the Protocol on Ireland/Northern Ireland.
At Biopharmaal Consulting, we specialise in helping GP sites achieve compliance and operational efficiency within these regulatory frameworks. This blog outlines the key differences between FDA, EMA, and MHRA regulations and their implications for GP sites conducting clinical trials.
1. Regulatory Framework and Oversight
FDA (U.S.)
- Governed by the Code of Federal Regulations (CFR), specifically 21 CFR Part 312 for Investigational New Drug (IND) applications.
- Clinical trials are approved and monitored by the FDA and Institutional Review Boards (IRBs).
EMA (Europe)
- Oversees the Clinical Trials Regulation (CTR) (EU) No. 536/2014, which harmonises trial approvals across EU member states as of 31 January 2022. The CTR replaced EU Clinical Trials Directive (Directive 2001/20/EC). The EU Clinical Trial Directive was repealed on 31 January 2022.
- National regulatory agencies handle individual country approvals, while the Clinical Trials Information System (CTIS) streamlines applications. CTIS is a single-entry point for sponsors and regulators to submit and assess clinical trial applications, facilitating faster and better assessments. All clinical trials; new or ongoing in the European Union (EU) after 30 January 2025 must comply with the Clinical Trials Regulation (CTR) and must have been submitted to the Clinical Trials Information System (CTIS).
MHRA (UK)
- Post-Brexit, the MHRA is responsible for all UK-based clinical trial approvals.
- The UK Clinical Trials Regulations were initially based on EU law but are now evolving separately.
- Applications are submitted through the Combined Review Service, which integrates regulatory and ethics approvals.
Clinical trial applications for investigational medicinal products (CTIMPs) and combined CTIMP and medical device trials are submitted through a combined review process using the Integrated Research Application System (IRAS). Only one application is required for Clinical Trial Authorisation (CTA) and Research Ethics Committee (REC) opinions.
Key Impact on GP Sites
- FDA: Requires GP sites to comply with a centralised but strict regulatory process.
- EMA: Standardised across the EU member states, but national variations still exist.
- MHRA: A standalone system that retains EU similarities but is moving towards a more streamlined UK-specific process.
2. Ethics Approvals and IRB/Ethics Committees
FDA: IRB Approval
Clinical trials must be approved by an Institutional Review Board (IRB), ensuring compliance with 21 CFR Part 50 (Informed Consent) and 21 CFR Part 56 (IRB Functions & Operations).
EMA: National Ethics Committees
- Ethics approval is handled at the national level within each EU member.
- The Clinical Trials Regulation (CTR) aims to streamline approvals via CTIS, but some country-specific variations remain.
MHRA: UK Ethics Committees (HRA & REC)
- Ethics approval is obtained through the Health Research Authority (HRA) and Research Ethics Committees (RECs).
- The MHRA’s Combined Review Service integrates regulatory and ethics approvals into a single application process.
Key Impact on GP Sites
- U.S. sites require IRB approval for each trial.
- EU sites must navigate national ethics approvals, which may differ by country.
- UK sites benefit from a streamlined combined ethics and regulatory review process.
3. Informed Consent Requirements
FDA: Paper-Based, Strict Documentation
- Written informed consent is mandatory under 21 CFR Part 50.
- Electronic consent (eConsent) is allowed but must comply with 21 CFR Part 11 (Electronic Records and Signatures).
EMA: ICH-GCP Compliant, e-Consenting Allowed
- The EU follows ICH-GCP (International Council for Harmonisation – Good Clinical Practice) standards.
- e-Consenting is increasingly accepted, but national regulations vary.
MHRA: Supports e-Consenting for Remote Trials
- The MHRA allows eConsent and supports its use in decentralised trials.
- Aligns with UK-specific Good Clinical Practice (GCP) standards, which are evolving post-Brexit.
Key Impact on GP Sites
- FDA requires strict documentation and compliance with Part 11 for eConsent.
- EU allows eConsent but with country-specific restrictions.
- The UK fully supports eConsent, making trials more adaptable for remote participation.
4. Safety Reporting and Adverse Event Handling
FDA: IND Safety Reports
- Investigators must report serious adverse events (SAEs) to sponsors immediately once they are made aware.
- Sponsors must file IND Safety Reports under 21 CFR 312.32.
EMA: EudraVigilance System
- SAEs and Suspected Unexpected Serious Adverse Reactions (SUSARs) are reported to the EMA by the sponsor via the EudraVigilance system
- SUSARs must be reported to EMA by sponsor within 7 days (fatal/life-threatening) or 15 days (non-fatal).
MHRA: Yellow Card System & SUSARs
- The UK uses the Yellow Card Scheme for adverse event reporting.
- SUSARs must be reported through the MHRA eSUSAR portal, by the sponsor, within 7- and 15-day timelines.
Key Impact on GP Sites
- FDA mandates direct IND safety reports.
- EMA centralises pharmacovigilance under EudraVigilance.
- MHRA uses the Yellow Card system and eSUSAR for reporting.
Pro Tip: Site must ensure they have a well established process for notifying the sponsor of any SAE/SUSARs using the SAE Reporting Form (typically provided by the sponsor) as soon as they become aware of an SAE. The process must be documented in a Standard Operating Procedure.
5. Inspections and Compliance Monitoring
FDA: BIMO Inspections
- The FDA’s Bioresearch Monitoring (BIMO) Program conducts site inspections.
- Non-compliance results in Form 483 citations, warning letters, or potential trial suspension.
EMA: National Inspections
- National regulatory agencies conduct inspections, with EMA oversight in specific cases.
- Focus on Good Clinical Practice (GCP) compliance.
MHRA: GCP Inspections
- MHRA conducts routine and for-cause GCP inspections.
- Non-compliance can lead to trials being suspended or regulatory action taken.
Key Impact on GP Sites
- FDA sites must prepare for direct BIMO inspections.
- EU sites undergo national inspections with some EMA oversight.
- UK sites are inspected under MHRA’s evolving post-Brexit GCP framework.
Each regulatory body presents unique challenges and compliance requirements for GP sites involved in clinical trials:
- FDA (U.S.): Centralised, strict compliance with CFR regulations, IND reporting, and BIMO inspections.
- EMA (EU): More harmonised under the new CTR, but national variations in ethics approvals and pharmacovigilance.
- MHRA (UK): Post-Brexit, the UK is moving towards a streamlined, efficient system with faster approvals and strong eConsent support.
At Biopharmaal Consulting, we help GP sites navigate these regulations, ensure compliance, and optimise their role in clinical research. Whether you’re conducting trials in the U.S., EU, or UK, our expertise ensures a smooth regulatory journey.
Need expert guidance for your GP site? Contact us today!