Types of inspection
There are three types of Good Clinical Practice (GCP) Inspections:
- Routine inspections: inspections of the systems and procedures used to conduct clinical research in the UK by both commercial and non-commercial organisations, in order to assure compliance with applicable legislation. Organisations are notified of routine inspections in advance.
- Triggered inspections: these are ad-hoc inspections that may be triggered as a result of MHRA licensing requests or reports received by the MHRA on suspected violations of legislation relating to the conduct of clinical trials. In rare circumstances the organisation may not be notified of these inspections in advance.
- Committee for Medicinal Products for Human Use (CHMP) requested inspections resulting from central marketing authorisation (MA) submissions: the CHMP can request GCP inspections in relation to marketing applications made using the EU centralised procedure. The European Medicines Agency (EMEA) coordinates these inspections, which are conducted by inspectors from the EU Member States. The MHRA GCP Inspectorate participated in the first EMEA-coordinated EU GCP inspection and, on request, continues to participate in EU GCP inspections (which are conducted both within and outside the EU).
Routine inspection process flowchart
A flowchart of the routine inspection process can be viewed using the link below.
GCP routine inspection process
(365Kb)
Submission of the requested information for routine inspections
Preliminary notification is sent out to those organisations identified for inspection. This request for information includes a list of clinical trials, organisation charts, standard operating procedure (SOP) lists and selected SOPs, key contact details, overview of facilities, key service providers and clinical trials activities. This should be a summary that can fit into one lever-arch file. The organisation supplies the dossier as requested by letter. The dossier is the basis on which the inspectors allocate resource, develop the inspection plan and set the provisional organisation fee category. The inspection plan is developed with the organisation to ensure all activities are covered and appropriate personnel are available for interview. A number of clinical trials are normally selected for detailed Trial Master File (TMF) review, although the inspection may not be limited to these.
GCP inspection dossier 
(260Kb)
GCP inspection dossier checklist (344Kb)
Clinical trial spreadsheet for GCP inspection dossier 
(29Kb)
GCP inspections: Further information (16Kb)
What to expect during a routine inspection
The inspections consist of site visits to the organisation and, where appropriate, selected clinical investigator sites. The inspection will start with an opening meeting where the lead inspector will outline the scope and purpose of the inspection, confirm the inspection plan and introduce the inspector(s). During the inspection, the inspectors will request additional documentation and the organisation should be prepared to provide this promptly during the inspection.
Interviews with relevant personnel, generally as per the inspection plan, are conducted. Time is built into the inspection for the review of documentation, for example the TMF for the selected clinical trials. The inspector may visit any facilities involved in clinical trials, for example data management units, archives, pharmacy and these visits may be pre-arranged by the inspector for logistical reasons or decided upon during the inspection. During the inspection, the inspectors reserve the right to change the inspection plan, for example additional interviews or time may be required dependent upon inspection findings.
At the end of the inspection there will be a closing meeting where the findings are reported verbally to the organisation, next steps given regarding any further sites to be inspected and the timescales for the report.
Findings and reporting of routine inspections
The grading of deficiencies found during inspection or subsequent to post-inspection review are classified as 'Critical', 'Major' and 'Other' findings (see definitions below). In addition, the inspectors will make some observations and recommendations in the report. The GCP inspectrate have in the past and continue to provide feedback on inspection findings at conferences and symposia. A summary of findings in GCP inspections undertaken during the period April 2007 to March 2008 can be found below.
GCP inspection findings classification (8Kb)
GCP inspections metrics report (198Kb)
Once the inspection has been completed an Inspection Report is prepared by the lead inspector after the last site visit or on receipt of the last document requested, which ever is later. It should be noted that the factual matter contained in the Inspection Report relates only to those things that the inspection team sees and hears during the inspection process. Once adequate responses have been received from the organisation, a closing letter and GCP Inspection Statement is issued. The Inspection Statement is not to be taken as implying a satisfactory state of affairs in documentation, premises, equipment, personnel or procedures not examined during the inspection.
Following the presentation at the GCP Seminar in October 2006 on providing suitable responses to GCP inspection findings, a guidance document can be found below:
Guidance for formulating responses to GCP inspection findings (29Kb)
Critical findings are routinely referred to the MHRA’s Clinical Trial Inspection Action Group (CTIAG), a non-statutory, multi-disciplinary group constituted to advise the Director of Inspection and Standards, the Director of Post-Licensing and the Director of Licensing on any recommendation for referral or enforcement action appropriate to the divisions, which arises from non-compliance detected during GCP inspections. CTIAG provides advice in cases where critical findings are identified during inspection and/or serious non-compliance is identified that could affect the rights, safety or well-being of trial subjects.
Triggered inspections
Triggered inspections differ from our routine systems based inspections, in that generally the objectives of the inspection are to answer specific questions raised or to satisfy the MHRA that a specific trial has been conducted in accordance with legislation stated above. The inspection activities at site will be similar, but these inspections can be unannounced and a plan may not be shared with the organisation.
