How to show MHRA you're meeting good clinical practice (GCP) standards and what to expect from an inspection.

Overview

Good clinical practice (GCP) is a set of internationally-recognised ethical and scientific quality requirements that must be followed when designing, conducting, recording and reporting clinical trials that involve people.

Organisations that may have to comply with GCP include:

  • pharmaceutical companies
  • contract research organisations
  • universities
  • NHS hospitals
  • charities
  • GP practices
  • clinical laboratories good laboratory practice

Guidance on good clinical practice. has been produced by the International conference on harmonisation of technical requirements for registration of pharmaceuticals for human use (ICH).

You can also get more information about GCP in the Good Clinical Practice Guide, produced by MHRA.

To ensure compliance with GCP, MHRA:

  • asks trial sites to notify them of serious breaches
  • carries out inspections of trial sites where serious breaches are reported
  • carries out inspections of trial sites that sponsor clinical trials, mostly based on a risk assessment score
  • carries out inspections of sites when companies apply for marketing authorisations

Report a serious breach

You must notify MHRA of serious breaches of GCP or the trial protocol. See Guidance for the notification of serious breaches of GCP or the trial protocol (PDF, 153KB, 14 pages) .

See the annual summary of MHRA GCP referrals.

Triggered inspections for serious breaches

MHRA may contact you to arrange an inspection if they suspect the law has been broken. This information might come from:

  • a serious breach notification
  • a whistleblower
  • other MHRA departments
  • the health research authority (HRA)

In rare circumstances, MHRA may give little or no notice of these inspections.

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 your organisation to conduct clinical trial research. The inspectors will select a number of your clinical trials to examine how your organisation’s trial procedures are applied. One or two investigator sites involved in the selected trials may also be inspected.

Trial-specific GCP inspections assess clinical trials that have been completed and reported.

Currently phase I units that are part of the phase I accreditation scheme are not part of the risk-based programme but they are inspected every 2 years.

The risk-based compliance programme uses information available to MHRA to determine an organisation’s risk. This information includes:

  • a compliance report
  • internal information about previous inspection history
  • organisational changes

Each organisation is given a risk assessment score and inspections are prioritised for the organisations with the highest risk assessment score.

This will be used with the output from the inspectorate risk-based progamme. A small number of the organisations in the medium and low-risk categories will be randomly selected for routine risk-based inspections.

See the flowchart of the inspection process (PDF, 32KB) .

Complete a compliance report

Organisations engaged in clinical trials are encouraged to complete a compliance report once every 2 years. Phase I units, clinical laboratories and individual investigators not acting as sponsors of clinical trials are not required to complete a compliance report.

Complete the compliance report (MS Excel Spreadsheet, 286KB) and send it to gcpriskbasedinspections@mhra.gsi.gov.uk.

Hard copies will not be accepted.

Compliance reports are not mandatory, but if you don’t submit one, you are more likely to get an inspection. This doesn’t apply if:

  • your organisation has submitted a compliance report (MS Excel Spreadsheet, 286KB) in the last 12 months
  • your organisation has been inspected between July 2013 and Septemer 2014 (excluding investigator site inspections)
  • your organisation is a clinic trial investigator hosting site (you are not acting as a sponsor for a clinical trial) with fewer than 20 non-commercial trials of investigational medicinal products
  • your organisation is a phase I unit
  • your organisation is a clinical laboratory
  • if you are an individual clinical investigator not acting as a trial sponsor

Pre-inspection documentation

You will be notified if your organisation is chosen for inspection under the routine risk-based inspection programme.

The notification includes a request for information, in the form of a GCP inspection dossier and a clinical trials spreadsheet to MHRA 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, 416KB) and the GCP inspection dossier clinical trial spreadsheet (MS Excel Spreadsheet, 110KB) to help you prepare your dossier. Use the GCP inspection dossier checklist (MS Word Document, 352KB) to ensure your dossier is complete.

MHRA will agree an inspection date and give you information on the inspection team and the practical logistical aspects of the inspection.

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 documents in it must be made available to the inspectors. This includes any electronic documents and emails. You’ll need to provide any equipment and software needed to access any electronic documents.

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 contract research organisation (CRO), then you will have to provide the TMF and/or other documents.

If you have problems meeting these requirements, you should tell the lead inspector before the inspection.

Failure to provide the TMF can affect the results of your inspection.

Inspections

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, floor plans etc. might be needed. All documentation requested should be provided 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.

An inspection plan will be given to you in advance and any comments or questions relating to it can be discussed with the lead inspector.

During the inspection

The inspection includes interviews with relevant people and a review of the documentation, such as the TMF. The inspector may visit:

  • data management units
  • archives
  • pharmacy
  • laboratories

You should be prepared to provide additional documentation to the inspectors on request.

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 for the report.

Grading of inspections findings

Deficiencies found during inspections are graded at 3 levels - critical, major and other.

The inspection report

The inspection report is emailed to you. You must respond to the report, see Guidance for formulating responses to GCP inspection findings (PDF, 42.4KB, 4 pages) . Your organisation must provide a response to the inspection report in the form of a corrective action and preventative action (CAPA) plan. 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, a GCP inspection statement will be issued to you by email.

Information from previous MHRA inspections.

Fees for GCP inspections

Fees for inspections

Make payment to MHRA

Feedback from GCP inspections

MHRA GCP inspectorate sent surveys to get feedback from inspected organisations and investigators. Organisations and investigators were asked to score their response to questions on the inspection process.

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.

GCP discussion forum

MHRA GCP forum MHRA GCP forum can help you comply with the clinical trials regulations and GCP requirements by. The forum gives you an opportunity to discuss clinical trials and GCP requirements with other researchers.

European and UK law and for GCP

You can find the European Union directives, GCP and other guidance in Volume 10 of the rules governing medicinal products in the European Union

The key UK legislation and guidance which covers GCP inspections includes:

Contact

For further information on GCP inspections, email info@mhra.gsi.gov.uk or clintrialhelpline@mhra.gsi.gov.uk