Good Clinical Practice (GCP) inspections

In general, the sponsor of a clinical trial will be notified 4-6 weeks in advance of a planned inspection. In relation to for cause or triggered inspections, a shorter notice period may be given. The notification will outline the trial that has been selected for inspection and the site(s) where the inspection will be conducted. It will also outline what will be reviewed as part of the inspection (the scope) and the planned number of inspection days. The notification will include an initial list of pre-inspection requests for information and documentation which must be provided to the HPRA in advance. This may include:

• Details relating to the number of trial participants involved at the site(s)
• Procedures outlining how the trial was to be conducted (e.g. standard operating procedures or SOPs)
• Trial-specific documents such as the protocol, informed consent forms, product handling instructions, laboratory manual, monitoring plans and reports
• CV of the Principal Investigator (the main doctor responsible for the conduct of the trial at the site) and key members of the clinical trial study team
• Access to electronic systems which may be used for the trial, in particular electronic health records if they are used for capturing relevant data
• Logistical details for travelling to the site

This information will be reviewed and used to develop an inspection plan, which will be provided to the site at least one week prior to the start of the inspection.

The duration of the inspection and the number of inspectors conducting it will vary depending on the complexity of the clinical trial and the activities conducted at the site. Typically, they are scheduled for 3-5 days and will be performed at the site that was chosen for the inspection. Where appropriate, certain types of inspections may also be conducted remotely.

The activities conducted during an inspection, including the type of documentation reviewed, will vary depending on the type of inspection and the scope. However, inspections usually consist of an opening meeting, document review, interview sessions with key personnel, a tour of facilities involved in the clinical trial and a closing meeting.

The scope and activities reviewed during some of the more common types of GCP inspections conducted by the HPRA are outlined below. This list is not exhaustive, but provides an overview of areas that would typically be reviewed.

Investigator site inspections may include a review of:

• Communication with the ethics committee / HPRA
• Conduct of the trial at the site
• Informed consent of trial participants
• Review of trial participant data
• Safety reporting
• Management of the investigational medicinal product(s)
• Facilities and equipment (including computerised systems)
• Management of biological samples
• Organisation of clinical trial documentation
• Monitoring

Sponsor (systems) inspections may include a review of:

• Organisation and personnel
• Facilities and equipment
• Standard operating procedures
• Set up, conduct and closure of clinical trials
• Monitoring
• Investigational medicinal product management
• Safety reporting
• Data management
• Reporting of clinical trial results
• Clinical trial documentation and archiving
• Sub-contracting and oversight of vendors
• Quality management system and audit

Sponsor (specific clinical trial) inspections may include a review of:

• Set up, conduct and closure of the clinical trial
• Monitoring
• Investigational medicinal product management
• Safety reporting
• Ongoing safety evaluation
• Data management
• Statistical analysis
• Reporting of clinical trial results
• Clinical trial documentation and archiving
• Quality management system/audit

A written report outlining issues identified during the inspection will be sent to the site / sponsor within three weeks of the end of the inspection.

Issues that are identified (also known as deficiencies) are classified into three categories: critical, major and minor. These are defined as follows:

Critical: Conditions, practices or processes that adversely affect the rights, safety or wellbeing of the subjects and/or the quality and integrity of data. Critical observations are considered totally unacceptable.

Major: Conditions, practices or processes that might adversely affect the rights, safety or wellbeing of the subjects and/or the quality and integrity of data. Major observations are serious deficiencies and are direct violations of GCP principles. 

Minor: Conditions, practices or processes that would not be expected to adversely affect the rights, safety or wellbeing of the subjects and/or the quality and integrity of data.

The site will be requested to provide a response to the issues outlined in the report within approximately three weeks of receipt. The report will outline the deadline for response and will contain a template to assist with responses. A response for each finding should be provided, outlining a root cause analysis of the deficiency (e.g. what caused the issue) and a proposal for corrective and preventative actions (CAPA). Specific actions are expected to be provided as part of this response, including what is going to be done, who will be responsible and when it will be completed. Further actions may be recommended by a Compliance Regulatory Group.

The responses will be reviewed by the inspection team to determine whether or not they are acceptable to address the issues identified and to prevent them occurring in future. The inspectors will routinely send follow up questions or request further clarification before the responses are finalised. When the responses to the inspection report are considered to be acceptable, the inspection can be closed and a close out letter is issued.