GCP inspections
GCP inspections for clinical trials
Inspections carried out in connection with clinical trials may concern either good manufacturing practice for the manufacture of investigational medicinal products or good clinical practice (GCP) as regards the conduct of clinical trials.
The details of procedures for verifying good clinical practice are laid down in Commission Implementing Regulation 2017/556.
GCP inspections for clinical trials as part of supervision
Fimea is responsible for the supervision of clinical trials in Finland and for compliance with EU and national laws in research work. According to the Clinical Trials Regulation, clinical trials must be conducted in line with the agreed trial protocol and with the principles of good clinical practice. For the purpose of supervision, Fimea may carry out GCP inspections pursuant to Article 78 of the Clinical Trial Regulation 536/2014.
GCP inspections may be carried out in the following situations (Article 2 of implementing regulation 2017/556):
a) before, during or after the conduct of a clinical trial;
b) as part of the verification of applications for marketing authorisation;
c) as a follow-up to the granting of marketing authorisations.
The annual plan for GCP inspections
Trials are selected for Fimea's annual GCP inspection plan based on the progress of trials initiated in Finland, questions related to marketing authorisation applications and other factors leading to a need for an inspection. The annual plan is therefore adapted and modified over time. The selection of medicinal products to be inspected is subject to a risk assessment in order to optimise the use of supervisory resources. Trial criteria used for the risk assessment relate to matters such as the stage, characteristics, the number of participants (age, other special populations) as well as any special aspects of the trial protocol.
The European Medicines Agency (EMA) coordinates the inspections carried out in the processing of centralised marketing authorisation applications (CAP), and the inspections may be carried out in either Member States or third countries. Inspections are normally carried out through cooperation between at least two Member States. Fimea's GCP inspectors participate in CAP inspections where resources allow.
Inspection types
An inspection may be either a routine inspection, the subject of which is selected according to predetermined criteria, or a triggered inspection arranged for a special reason.
The target of the inspection is the trial itself and may involve inspecting the activities of any party involved in carrying out the trial. The inspection may be carried out at the site where the subjects are treated (investigator site), the site of an organisation commissioned to be involved in the trial (e.g. Clinical Research Organisation) or the site of the trial’s sponsor.
Currently, inspections can also be carried out remotely either in whole or in part.
Inspection procedure
Inspection planning and notification
Fimea's inspection team consists of a lead inspector, who serves as the primary contact between the inspectee and the agency, as well as other inspectors and experts. There may also be observers participating in the inspection.
The lead inspector contacts the contact person for the trial normally a few weeks before the planned inspection to notify them of the planned inspection date. The inspection can also be carried out without a prior notice. A written inspection announcement confirms the date and place of the inspection. This announcement contains a list of the material submitted to Fimea in advance. The members of the inspection team should also have (read-only) access to the electronic systems used in the trial, such as the electronic case report forms and the trial master file.
If the inspection is carried out remotely either completely or in part, advance testing is arranged with the inspectee for both the needed video-conferencing systems as well as platforms used for the submission of documents (secure e-mail, electronic portal, etc.).
Inspection
The inspection’s initial meeting consists of discussion of the inspection schedule and content. Inspections involve interviewing trial personnel and examining research-related documents (including patient documents). The trial facilities and equipment are also inspected. Inspectors have the right to take visual recordings during the inspection.
During the inspection, someone must be available who can provide explanations to the inspectors and is familiar with the research documents.
In the closing meeting, the inspectors share their findings. If any issues remain unresolved after the inspection and the inspector has not received satisfactory answers, the inspectee(s) may be requested to provide further clarification.
Inspection report
The inspection team draw up an inspection report with a description of the observations on findings. Findings are classified as critical, major or minor depending on their impact on the safety, well-being and rights of the subjects or the reliability of the research results.
When the inspection report has been signed at Fimea, the lead inspector sends a copy to the sponsor, the agreed contact person and, in cases where the inspection has been carried out at the investigator site, the investigator as well. The inspectee has the opportunity to make a statement on the report. In this statement, the inspectee may indicate where they disagree with the report. In addition, the inspectors may request further clarification from the inspectee concerning the findings identified in the report. The inspectee is requested to provide a plan of corrective and preventive actions at least in relation to the findings identified as serious or critical.
The inspectee's statement and further clarifications, as well as the inspection team's assessment thereof, are attached to the final inspection report.
Where several separate inspections are carried out on the same trial, a summary report may be drawn up summarising the findings of the separate inspections.
The GCP inspection is considered complete when the statement of the inspectee and any further clarifications have been assessed by Fimea. The assessment is also attached to the report and copied to the inspectee and the sponsor.
The documents related to the inspection are archived in accordance with Fimea's filing plan (in the case management system).
Communication of inspection results and follow-up supervision
The results of GCP inspections are reported to the EU Clinical Trials Information System (CTIS). The inspection reports are made public. The reports published in the EU database take into account data confidentiality as defined in Article 81(4) of the Clinical Trial Regulation.
Corrective and preventive measures must be taken in response to findings identified during inspections. Where necessary, Fimea may supervise their implementation through measures such as additional inspections.
If the inspection reveals serious or critical deficiencies that relate to subject safety or data reliability, the follow-up measures may involve discontinuing the trial or demanding modifications to some particular aspects. In the case of applications for marketing authorisation, the findings may mean either a need for clarifications or the rejection of the application. Fimea officials carry out any further measures in line with the organisation’s rules of procedure.
Ask more
Sarianne Päivike, senior inspector, tel. +358 29 522 3233
Anne Timonen, senior inspector, tel. 358 29 522 3375
E-mail addresses follow the form [email protected]