Clinical trials for medicines: Good clinical practice inspections
Information relating to good clinical practice (GCP) inspections.
The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) has produced guidance on Good Clinical Practice (ICH E6 (R3)).
Good clinical practice (GCP) is an ethical and scientific quality guideline concerning the design, conduct, analysis and reporting of clinical trials of medicines.
ICH E6 (R3) Good Clinical practice is composed of overarching principles, Annex 1 (interventional clinical trials), Annex 2 (additional considerations for non-traditional interventional clinical trials), Glossary and Appendices.
For more information on implementation of ICH E6 (R3) GCP in the UK see guidance on compliance with ICH E6 good clinical practice (GCP) in the United Kingdom and for UK specific annotations to ICH E6 (R3) see UK-specific annotations to ICH E6(R3) .
Organisations that have to comply with GCP as set out in the MHRA guidance above include:
- pharmaceutical companies
- organisations who provide services to undertake any function of the sponsor and investigator conducting clinical trials (e.g. contract research organisations, organisations who develop and maintain trial specific computerised systems)
- universities
- NHS hospitals
- charities
- GP practices
- laboratories analysing samples originating from a clinical trial (including NHS, academic and commercial laboratories)
To support compliance with GCP, the MHRA:
- requires organisations sponsoring clinical trials to notify them of serious breaches
- may conduct triggered inspections of organisations where serious breaches are suspected
- may conduct routine risk-based inspections of organisations that sponsor or conduct clinical trials
- may conduct inspections of clinical trials, and associated activities, submitted in support of a marketing authorisation application
Compliance with GCP
You must notify us of serious breaches of GCP or the trial protocol. See Guidance for the notification of serious breaches of GCP or the trial protocol
See the annual summary of MHRA GCP referrals.
Inspections under the risk-based compliance programme
The majority of MHRA GCP inspections are carried out under the risk-based compliance programme. These can be either systems-based or trial specific.
GCP systems inspections examine the systems used by an organisation to conduct clinical trial research. The inspectors will select a number of clinical trials to examine how the organisation’s trial procedures are applied. 1 or 2 investigator sites involved in the selected trials may also be inspected.
Trial-specific GCP inspections assess an individual clinical trial and any organisation involved in the trial may take place. These may be risk-based routine inspections or concern a trial that has been submitted as part of an application for a marketing authorisation.
Additionally, phase I units that are part of the phase I accreditation scheme are regularly inspected to assess compliance with the requirements of the scheme. Inspections may also be conducted to assess trial conduct and compliance with GCP and regulatory requirements.
The risk-based inspection programme uses information available to the MHRA to determine an organisation’s risk. This information includes:
- internal information including, clinical trial applications, marketing authorisation applications, previous compliance and inspection history
- organisational changes
- intelligence from external sources
Routine GCP inspections are conducted as per the diagram below, and more detail is provided in the sections below for each step. This figure shows the typical steps for planning, conducting, and reporting an inspection, though the order may vary.
Triggered inspections
An organisation may be contacted to arrange an inspection if we suspect the law has been broken. This information might come from:
- a serious breach notification
- a whistleblower
- other MHRA departments
- other regulatory intelligence
- the health research authority (HRA)
In rare circumstances, we may give little or no notice of these inspections.
Pre-inspection documentation
We will notify you if your organisation is chosen for inspection unless the inspection is to be conducted with no notice.
The notification includes a request for information, in the form of a GCP inspection dossier and a clinical trials spreadsheet within 30 days.
This dossier should include:
- a list of clinical trials
- organisation charts
- standard operating procedure (SOP) lists
- contact details
- overview of facilities
- service providers
- clinical trials activities
Use the GCP inspection dossier template (MS Word Document, 153 KB) and the GCP inspection dossier clinical trial spreadsheet (MS Excel Spreadsheet, 35 KB)to help you prepare your dossier. Use the GCP inspection dossier checklist (MS Word Document, 181 KB) to ensure your dossier is complete.
An inspection date will be arranged, and you will receive details about the inspection team as well as practical information regarding the logistics. While we strive to select a date that suits everyone, circumstances may require us to set the inspection date if no mutual agreement is reached.
Occasionally, after reviewing the dossier, the lead inspector may decide not to proceed with the inspection.
The trial master file (TMF)
A number of clinical trials are usually selected for trial master file (TMF) review, although the inspection may not be limited to these.
The complete TMF is the basis for inspection and all the records in it must be made available to the inspectors. This includes any electronic records and emails. You’ll need to provide any equipment and software needed to access any electronic records. Where multiple electronic systems constitute the complete TMF direct access must be made available to each system.
You can discuss with the lead inspector beforehand on how to make the TMF available during the inspection.
If you are a sponsor and have subcontracted some activities to a service provider, then the organisation will need to provide access to the TMF and/or other records.
If you have problems meeting these requirements, you should tell the lead inspector before the inspection.
Failure to provide the TMF will affect the results of your inspection.
The inspection plan
The inspection plan is based on discussions with you and the information provided in your GCP inspection dossier, to ensure all activities are covered. Appropriate people should be available for interview either in person or by teleconference.
Additional supporting documentation such as line listings, database extracts and floor plans. might be needed. You should provide all documentation requested within the time agreed with the lead inspector.
Inspectors will be flexible with the inspection plan to accommodate working patterns of individuals and immediate issues if they arise.
You will receive an inspection plan in advance of the inspection unless it is a short or no notice inspection. You can discuss any comments or questions relating to with the lead inspector.
During the inspection
The inspection includes interviews with relevant people and a review of the documentation, such as the TMF. You should be prepared to provide additional documentation to the inspectors on request. The inspector may visit any relevant departments during an on-site inspection.
Inspection findings
At the end of the inspection the inspector will give you a verbal summary of the inspection findings and allow you the opportunity to correct any misunderstandings. The grading of the findings are provisional and may be changed by the inspector when compiling the report.
Grading of inspections findings
Deficiencies found during inspections are graded at 3 levels: critical, major and other.
Critical
a) Where evidence exists that significant and unjustified departure(s) from applicable legislative requirements has occurred with evidence that:
- the rights, safety or well-being of trial subjects either has been or has significant potential to be jeopardised, and/or
- the clinical trial data are unreliable and/or
- there are a number of Major non-compliances (defined in (d) and (e)) across areas of responsibility, indicating a systematic quality assurance failure, and/or
b) Where inappropriate, insufficient or untimely corrective action has taken place regarding previously reported major non-compliances (defined in (d) and (e)).
c) Where provision of the TMF does not comply with Regulation 31A 1-3, as the TMF is not readily available or accessible, or the TMF is incomplete to such an extent that it cannot form the basis of inspection and therefore impedes or obstructs inspectors carrying out their duties in verifying compliance with the regulations.
Major
d) A non-critical finding where evidence exists that a significant and unjustified departure from applicable legislative requirements has occurred that may not have developed into a critical issue, but may have the potential to do so unless addressed, and/or
e) Where evidence exists that a number of departures from applicable legislative requirements and/or established GCP guidelines have occurred within a single area of responsibility, indicating a systematic quality assurance failure.
Other
f) Where evidence exists that a departure from applicable legislative requirements and/or established GCP guidelines and/or procedural requirement and/or good clinical practice has occurred, but it is neither critical nor major.
The inspection report
The inspection report is emailed to the organisation inspection host. You must respond to the report. Your organisation must provide a response to the inspection report in the form of a corrective action and preventative action (CAPA) plan, see CAPA guidance for formulating responses to GCP inspection findings (MS Word Document, 75.8 KB). In response to inspection finding the organisation may be required to complete an impact assessment, details of any requirement in this regard will be included in the report. For some inspections, you may need to provide periodic reports on the progress of proposed CAPA actions.
The lead inspector may ask you for additional clarification from the responses you provided. Usually, you will be given one opportunity to provide additional information or clarification.
Once adequate responses are received, you will receive a GCP inspection statement by email.
Actions after the inspection
If critical findings are identified, these are referred to the GCP Inspection Action Group (IAG2). This is a cross-agency group that oversees all critical findings and decides on the actions to be taken in addition to the review of the CAPA for the critical finding.
There are a number of possible non-routine post-inspection actions that the IAG may consider, depending on the critical finding and the impact on public safety and data integrity. These include:
- periodic reporting
- early re-inspection
- referral to relevant stakeholders (for example, other regulators/agencies, Health Research Authority (HRA), General Medical Council (GMC), Care Quality Commission (CQC))
- suspension of CTA(s)
- an infringement notice
- prosecution
Fees for GCP inspections
GCP inspection metrics
To help you understand the areas where GCP inspectors have found compliance problems during GCP inspections in the UK, the GCP inspectorate produces metrics reports.
Infringement notices
An infringement notice may be issued when instances of serious or serious and persistent non-compliance with GCP requirements have been identified.
Below are all the infringement notices that have been issued for GCP. Some information may be redacted. Redacted information contains elements of personal data, the disclosure of which would be unfair in that it would breach the first principle of the Data Protection Act which says that information must be processed fairly and lawfully
| Organisation / Person | Date Issued | Reason | Status |
|---|---|---|---|
| Celixir | 17 July 2024 | Regulatory Action | Celixir acknowledged the findings of the MHRA’s inspection and proposed a set of corrective and preventative actions (CAPAs) which were comprehensive and included effective measures to ensure the compliance with GCP and trial authorisations and the conformity of the Investigational Medicinal Product Dossier (IMPD) as stated in the Notice and that future clinical trial activity involving Celixir is conducted in a manner that is fully compliant with the Regulations. During this process, Celixir provided all the information to the MHRA and does not hold any information to identify the patient who was dosed (with placebo). The implementation of the CAPAs and compliance with GCP has been independently audited and confirmed by a specialist GCP auditor who has been retained to ensure Celixir’s continued compliance with GCP, trial authorisations and the conformity of the IMPD. |
| Dr David Connell | 14 March 2016 | Regulatory Action | Dr Connell responded to the Infringement notice to confirm that he has relinquished his license to practice medicine in the UK and has no intentions of practicing medicine again in the UK. Dr Connell has confirmed that if he does take part in clinical trials in the UK in the future, he will comply with the conditions of the infringement notice. Dr Connell also confirmed that he did not retain any data or documents from the trials in question, therefore the MHRA also wish to highlight that without any retained data it is not possible to verify the conclusions published from this clinical trial. |
| Mrs Zirka Yousaf | 1 July 2016 | Regulatory Action | Mrs Zirka Yousaf responded to the Infringement Notice to confirm she has implemented an SOP and checklist to ensure future work is adequately documented, will ensure future work commitments are feasible and will not outsource or subcontract work to another contractor. Mrs Zirka Yousaf has confirmed that she will comply with the conditions of the infringement notice. MHRA has verified that there is no impact on patient safety. However, MHRA would also like to remind sponsors that they are ultimately responsible for GCP. Therefore, sponsors have a requirement to ensure oversight of all staff working on their trials, including contractors and those that may be home based. Suitably robust contracts and adequate oversight mechanisms could identify and therefore reduce the likelihood of the non-compliances observed in this infringement notice. |
| Dr Jerome Kerrane | 9 November 2017 | Regulatory Action | Dr Kerrane responded to the Infringement notice to confirm that he has undertaken further training associated with GCP, information governance and financial probity. Dr Kerrane has confirmed that he has not taken part in clinical trial activities since 2015 and has no intentions of undertaking trial work in the future. The MHRA would like to remind investigators of the requirement to comply with the approved trial protocol to ensure the safety of trial participants and the integrity of the data collected; and trial sponsors of the need for effective monitoring. |
Infringement letters
Celixir infringement notice (PDF, 112 KB, 3 pages)
Mrs Zirka Yousaf Infringement Notice (PDF, 3.97 MB, 11 pages )
Dr Jerome Kerrane Infringement Notice (PDF, 1.22 MB, 3 pages)
Dr David Connell infringement notice (PDF, 786 KB, 2 pages)
Oversight and monitoring of clinical trials
This guidance is currently under review, updated guidance will be posted to the clinical trials hub in due course.
To assist sponsors and those conducting trials, we have produced guidance on oversight and monitoring processes, including risk-based monitoring.
On-site access to electronic health records by sponsor representatives in clinical trials
This guidance is currently under review, updated guidance will be posted to the clinical trials hub in due course.
We have also published guidance on on-site access to electronic health records.
Contact
If you have any questions or concerns regarding your GCP inspection, direct them to the lead inspector, one of the assisting inspectors, or the GCP operations manager.
For further information on GCP inspections, or GCP compliance email info@mhra.gov.uk or ctdhelpline@mhra.gov.uk
Updates to this page
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This page has been updated to streamline and clarify information in light of recent changes to clinical trials legislation. Content has been reorganised, references updated (including to ICH E6 (R3)), and links improved to direct users to current online guidance. The amended Clinical Trials Regulations took full effect on 28 April 2026. As such, this guidance should now be considered effective and is no longer in draft.
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Updated to attach new CAPA guidance for formulating responses to GCP inspection findings - file attachment
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Updated pre inspection information and add 2 new files GCP inspection dossier template and GCP inspection dossier checklist.
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Updated GCP inspection dossier clinical trial spreadsheet.
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An infringement notice has been added for Celixir.
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Updated 'GCP inspection dossier clinical trial spreadsheet'
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GCP inspection dossier clinical trial spreadsheet updated.
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Updated CAPA guidance PDF
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Added links for: Risk-Adapted Approach to clinical trials and Risk Assessments Oversight and monitoring of investigational medical product trials
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MHRA StEM March 2021 minutes and slides uploaded
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Replaced the GCP inspection dossier clinical trial spreadsheet with a new version
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Uploaded new versions of the Guidance for the notification of serious breaches of GCP or the trial protocol, and the notification of serious breaches of GCP or the trial protocol form.
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GCP Dossier clinical trials spreadsheet update
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Added a single line confirming that, in a no-deal Brexit, the MHRA’s GxP risk-based inspection programmes will remain unchanged.
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We have updated the attachments for the MHRA GCP Laboratories Stakeholders Engagement Meeting
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We have added in meeting minutes and the presentation from the GCP Stakeholder Engagement Meeting
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Added minutes and presentations from the May 2019 Stakeholder Engagement meeting.
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Updated contact email address
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Update of notification of serious breaches of GCP or the trial protocol form
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Added a new section on Inspection Outcomes.
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Added third entry into table under Infringement Notice
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Updated Serious Breach reporting form.
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StEM November 2017 summary and slides attached
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Updated the serious breach notification form.
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Updated the link to the Good Clinical Practice Guide.
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New spreadsheet added for GCP inspection dossier clinical trials.
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Information on infringements
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Updated inspection checklist
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Added presentations and case studies from the GCP Stakeholder Engagement Meeting in March 2016.
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Added GCP Stakeholder Engagement Meeting minutes.
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Update to requirements for completing a compliance report in 2016.
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First published.