Good Clinical Practice: Risk based inspections

Background
Over the past three years, in the UK there have been significant developments in inspection risk management and the strategies of a number of regulators were reviewed by the MHRA.

It is considered that the scope, frequency and depth of inspections should be dependent on how the regulated organisation takes responsibility for compliance with the regulations. Whilst the company or organisation has always had legal responsibility for compliance, the notice of inspection has for some been a trigger for compliance assessment instead of a continuous compliance programme being in place.

Following a detailed review of risk based inspection models used by a range of organisations, a draft model was designed to cover all GxP inspections, however, at implementation it is envisaged that there will be a different emphasis within the individual elements as appropriate to the different GxPs.

Risk-based inspection process
The GCP Risk Based Inspection Process commences for all organisations (sponsors, contract research organisations, hosting trial sites) that are engaged in clinical trial activities in the UK, from 15 May 2009. It uses a combination of information provided to the MHRA on the Compliance Report, internal information about previous inspection history, organisational changes and other compliance reports with the results of intelligence gathering to determine an organisation’s control of their risk.

The resulting risk assessments will be categorised into high, medium and low risk and inspections prioritised for the companies with the highest risk category. For internal control purpose, a small proportion of organisations from the medium and low risk categories will be randomly selected for inspection. Inspections will be planned according to how much inspection resource is available in the upcoming year. The results of the compliance report being used to determine an approximate amount of inspection time required to perform the inspection.

Completion of the Compliance Report by sponsors, contract research organisation (CRO) or hosting sites is not mandatory. However, these organisations should be aware that failure to submit a Completed Report will be assigned to a high risk category. Currently, Phase 1 units and individual investigators not acting as sponsors of clinical trials are not required to complete the compliance report.

The results of the risk assessment will be provided to the organisation. If there are any concerns regarding the risk assessment this should be send to the GCP risk based inspection mailbox (gcpriskbasedinspections@mhra.gsi.gov.uk).

Compliance report
Organisations engaged in clinical trials will be encouraged to complete a Compliance Report as an annual activity. The MS-Excel versions of the Compliance Report can be found on the right-hand side of this page for download. The Compliance Report contains detailed guidance on the terms used in the questions. The Compliance Report should be returned to the GCP risk based inspection mailbox in electronic form. The compliance report template had some minor revisions on 11 June 2009.

Inspection process
The inspection process will be largely indistinguishable from that operated in recent years. Once the risk assessment has been determined and an inspection scheduled, the organisation to be inspected will be contacted and requested to complete a Summary of Clinical Trials System (SCTS) as previously. The reason for continuing with provision of the SCTS is that this contains the detailed information about how the organisation operates, which is used for inspection preparation rather than planning. The inspection will then be undertaken as previously and will conclude as usual with a closing meeting where findings are verbally reported to authorisation holder contacts. Further information on the inspection process can be found on the GCP web page.

Any questions or comments on risk based inspection should be addressed to the GCP risk based inspection mailbox (gcpriskbasedinspections@mhra.gsi.gov.uk) in the first instance. You may also wish consult the FAQ (top right), as this may answer your question(s).

What should UK clinical trials organisations do next?
Step 1: Download MS-Excel versions of the Compliance Report from the MHRA GCP web pages.

Step 2: Complete the Compliance Report (someone within the organisation should have specific responsibility for this task to avoid duplicate submissions).

Step 3: Submit the completed Compliance Report electronically to gcpriskbasedinspections@mhra.gsi.gov.uk by 30 June 2009. Questions about the Compliance Report should also be submitted to the mailbox.