The TGA has published new guidance entitled Good Clinical Practice (GCP) inspection program – Guidance for GCP inspection of clinical trial sites for investigational biologicals and medicinal products
Clinical trials of medicines and biologicals regulated under the Clinical Trial Notification (CTN) or Clinical Tiral Approval (CTA) schemes are subject to the TGA’s Good Clinical Practice (GCP) Inspection Program.
What is GCP?
Good Clinical Practice (GCP) is an international ethical and scientific quality standard for designing, conducting, recording and reporting clinical trials. Compliance with GCP provides assurance that the rights, safety and well-being of clinical trial participants are protected and that the trial data generated are credible.
For investigational medicinal products and investigational biologicals, the TGA recognises the following internationally accepted GCP guideline: International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Guideline for Good Clinical Practice with TGA annotations.
The TGA GCP inspection program
Clinical trials of medicines and biologicals regulated under the CTN or CTA schemes are subject to the TGA’s Good Clinical Practice (GCP) Inspection Program.
The TGA inspects Australian clinical trial investigator sites of clinical trials for medicines and biologicals to assess whether they are meeting their GCP responsibilities.
Following a successful pilot program, the TGA is implementing the ongoing risk-based Good Clinical Practice (GCP) Inspection Program.
What are the objectives Objectives of the Good Clinical Practice (GCP) inspection program?
The GCP inspection program aims to strengthen the TGA’s monitoring activities and protect bpublic health. GCP inspections allow the TGA to:
- verify that you are compliant with the GCP standard and have met your clinical trial responsibilities
- provide education and work with you to ensure you have effective systems in place in alignment with Australian legislation and the relevant GCP guideline(s).
- provide information (if appropriate) relating to the inspection findings to the approving authority and/or the approving HREC
What is the scope of the GCP inspection program?
All Australian investigator sites involved in regulated clinical trials of medicines and biologicals
are subject to the GCP inspection program.
Inspections will examine your compliance with the followig applicable Australian legislation and
guideline(s):
• Therapeutic Goods Act 1989 (the Act)
• Therapeutic Goods Regulations 1990 (the Regulations)
• the GCP guideline(s).
What does the new guidance describe?
The new guidance describes the following:
- how the TGA prioritises and schedule GCP inspections
- the kinds of inspections that the TGA might conduct
- the inspection process, and
- how TGA reports and follows up on inspections.
Some of the information from the guidance is provided below.
Inspection prioritisation
The TGA’s GCP inspection program has been designed to be harmonised with current international approaches, with a particular focus on early phase trials of new medicines or of combinations of medicines, or where there may be safety or other concerns.
TGA takes a a risk-based approach to selecting sites for GCP inspections.
- Trials with higher risk are more likely to be inspected.
- The majority of GCP inspections will be trial specific, routineinspections of clinical trials that have been completed and reported.
- However, other types of inspections including random inspections as well as ‘for cause’ inspections may also occur.
- The selection of clinical trials for inspection is based on risk assessment proposed by the National Health and Medical Research Council (NHMRC) in Risk-based Management and Monitoring of Clinical Trials Involving Therapeutic Goods 2018
Inspection risk criteria
The risk criteria fall into 2 categories:
- investigational medicinal product (IMP)
- trial conduct, design, and methods.
In addition, TGA will consider other elements, including but not limited to the following:
- type of site i.e., located at large institution vs. small clinic
- geographic location i.e., sites selected throughout the region
- number of participants screened, enrolled, and withdrawn for the trials at the site
- compliance history of the investigator sites and sponsor, including findings from previous GCP inspections of investigator sites.
Types of Inspections
The following are the types of inspections that the TGA might conduct:
- Routine inspections
- ‘For cause’ inspections
- are undertaken in response to specific triggers where a GCP inspection is the appropriate way to examine the issues.
- They generally focus on specific aspects of the clinical trial at a particular investigator site or examine identified compliance issues and their impact
- Significant safety concerns or identified noncompliance are expected to be the most common triggers.
- Announced and unannnnounced inspections
- Reinspections
- Remote inspections
How prepare for inspection
If you have been notified of a GCP inspection, you should prepare for the inspection by:
- ensuring your authorising institution, trial sponsor and clinical team are advised of the inspection
- ensuring access for the inspectors to clinical trial records and source documents is arrang for the time of the inspection.
TGA will:
- avoid duplicating inspections conducted as part of another country’s GCP inspection program when feasible.
- prepare an inspection plan, which will identify:
- the objectives and scope of the inspection
- our inspection team member(s) and their respective role(s)
- the inspection date and site(s) to be inspected
- the specific documents, electronic tools, and systems to be reviewed and which we require access to
- the expected time and duration of each major inspection activity.
Conducting the inspection
The inspection will proceed according to the details set out in the inspection plan. This will be negotiated prior to the inspection and can be amended during the inspection to ensure that TGA achieves the inspection objectives. Any amendment to the plan will be documented. The inspection will take place over several days, typically 3 consecutive days, depending on the complexity of the trial.
Grading deficiencies
Deficines may be graded as follows:
- Critical deficiency
- Major deficinecy
- Minor deficiency
Inspection reports
The TGAs inspection team will prepare an inspection report and associated close-out record for each GCP inspection.
The TGAs inspectors will usually issue you the GCP inspection report and cover letter within 30 days of completing the inspection.
- If an inspection identifies deficiencies, TGA will ask you to prepare a corrective and preventative actions (CAPA) plan in the form of a close-out record on the template provided with the inspection report.
- You should provide the inspectors with the close-out record within 30 days of receiving the inspection report.
- When you submit the close-out record, you should also comment on any major factual errors in the inspection report.
- If TGA does not receive your response within the agreed time frame, this will be recorded in the inspection report
- The TGA inspectors will assess the close-out record. We will correct any major factual errors in the final inspection report.
- The TGA will:
- assess the impact of any comments on the inspection findings and the adequacy of the proposed CAPA and proposed time frames.
- document our assessment of the CAPA in the close-out record. If we do not accept your proposed CAPA or timeframes for actions, additional follow-up will occur to reach an agreement.
- close the inspection when we have agreed on an acceptable CAPA plan. The lead
- inspector will sign the final inspection report and associated close-out record and issue these to you.
- The TGA inspectors inspectors may ask you for ongoing evidence of completion or updates on your CAPA activities.
Inspection follow-up
If TGA identifies non-compliance with any of the folllowing, it will follow up with you until you complete a CAPA plan that appropriately addresses the non-compliance.
- the study protocol,
- the GCP guideline(s) or
- the National Statement,
TGA may undertake one or more of the following follow-up actions:
- meeting with you to discuss the deficiencies, their impact, and your action plans
- reviewing progress reports on the corrective actions
- re-inspecting to assess appropriate implementation of the CAPA plan
- asking you to provide it with data you have not yet submitted
- communicating the inspection findings to other regulatory authorities, where applicable under international agreements.
Further information
An education webinar was held on Monday 9 May 2022 to provide an overview of this new guidance and the GCP Inspection program. Here is a link to the presentation from the webinar.