UK MHRA Guidance: Meeting MHRA’s Good Clinical Practice (GCP) Standards: A Practical Guide to Preparation, Compliance, and Inspection Expectations

Good Clinical Practice (GCP) serves as the foundational ethical and scientific standard that governs how clinical trials involving human participants are designed, conducted, recorded, and reported. In the United Kingdom, the Medicines and Healthcare products Regulatory Agency (MHRA) enforces these standards to protect participant safety and the integrity of clinical data. The official guidance on Good clinical practice for clinical trials explains how sponsors, investigators, and trial sites should demonstrate compliance with GCP and outlines what to expect during an MHRA inspection.

Most recently updated on 12 December 2025, this guidance incorporates pre-inspection information and adds two new supporting documents: the GCP inspection dossier template and the GCP inspection dossier checklist, which serve as essential tools for inspection readiness.

What Good Clinical Practice Means in the MHRA Context

MHRA describes GCP as a set of internationally recognised ethical and scientific quality requirements that apply to all clinical trials involving people. These requirements ensure that the rights, safety, dignity, and well-being of trial participants are upheld and that the data generated are reliable, robust, and acceptable for regulatory decision-making. The principles build on the ICH GCP framework, which is widely accepted among regulators globally.

In practical terms, this means that anyone involved in a clinical trial—whether they are part of a pharmaceutical company, a contract research organisation (CRO), an academic institution, an NHS hospital, or a commercial laboratory analysing trial samples—must adhere to the same core GCP principles and be ready to justify their compliance to MHRA inspectors at any time.

Preparing for a GCP Inspection: Pre-Inspection Documentation

MHRA uses a risk-based compliance programme to prioritise inspections and may conduct routine, for-cause, or triggered inspections depending on reports of serious breaches or other risk indicators. MHRA expects organisations to be continually inspection-ready, with structured documentation that demonstrates compliance with all elements of GCP.

To support this, the 2025 guidance provides an updated set of pre-inspection information requirements and two new supportive tools: the GCP inspection dossier template and the GCP inspection dossier checklist. These documents help sponsorship teams compile all essential materials before an inspector arrives, making preparation systematic rather than reactive.

The dossier template and checklist act as overarching frameworks to organise trial documentation coherently. They cover all aspects of a clinical trial, including governance files, trial master files (TMF), investigator site files, safety reporting documents, monitoring records, quality assurance records, and evidence of ethics approvals. Using these tools helps ensure that the inspection team can quickly locate critical information and verify the trial’s compliance with GCP.

What Inspectors Look for During a GCP Inspection

During an inspection, MHRA will focus on key components of trial conduct, with particular attention to participant safety, data integrity, and ethical compliance. Inspectors assess how well the sponsor’s and investigator’s quality systems have translated into consistent practices across trial sites and activities.

Specifically, inspectors will examine how:

• The trial master file was created and maintained, including completeness, organisation, and traceability of key documents such as the protocol, amendments, ethics committee correspondence, informed consent forms, and essential regulatory submissions.

• Informed consent was obtained and documented for every participant, ensuring that consent was given freely and that participants were fully informed about risks, benefits, and trial procedures.

• Qualifications and training of investigators and clinical staff are documented and maintained, including evidence of GCP training and role-specific competence.

• Safety reporting procedures are implemented, particularly for serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs), with appropriate escalation to regulatory authorities and ethics committees.

• Monitoring plans and oversight activities are executed in accordance with the risk-based monitoring strategy, including on-site or remote source data verification and corrective actions for non-compliance.

• Deviation and violation handling processes are documented, with records of how deviations were identified, reported, assessed for impact, and resolved.

The inspection is not meant to be a punitive exercise but rather an objective evaluation of whether the conduct and documentation of the clinical trial align with regulatory expectations and protect the rights and well-being of participants.

Actions After an Inspection

At the conclusion of an inspection, MHRA will typically discuss initial observations with the sponsor or clinical site representatives. This may be followed by a written report that outlines any findings, recommendations, or required corrective and preventive actions (CAPAs). Depending on the severity of any deficiencies, MHRA may request follow-up evidence demonstrating how corrective actions have been implemented or may take regulatory enforcement actions if compliance gaps significantly impact participant safety or data quality.

Inspections can also produce infringement notices or infringement letters when formal regulatory non-compliance is identified, and these outcomes compel organisations to strengthen quality systems before future trials or inspections.

Incorporating Risk-Adaptive Approaches and Oversight

The updated guidance reaffirms MHRA’s encouragement for sponsors to adopt risk-based approaches in both trial management and inspection preparation. This aligns with contemporary international trends, such as those reflected in the evolving ICH E6(R3) GCP guideline, which emphasises proportionate quality management, risk-based monitoring, and a modern framework for trial conduct.

Risk-adapted oversight ensures that resources are directed toward areas that are most critical to trial integrity and participant protection, such as enrolment processes, consent documentation, investigational medical product accountability, and safety event handling.

By embracing risk-based approaches, maintaining organised documentation, and using the updated inspection dossier template and checklist, sponsors and trial sites can ensure that they meet regulatory expectations and protect participant well-being throughout the lifecycle of a clinical trial.

For more information, see the official guidance: Good clinical practice for clinical trials