Good Clinical Practice Inspection Program: Frequently asked questions
These FAQs should be read in conjunction with the Guidance for GCP inspection of clinical trial sites for investigational biologicals and medicinal products. They address questions raised by attendees at TGA webinars held in May and June 2022 about the inspection program. If you have further questions please contact GCP.Inspection@health.gov.au.
Voluntary GCP inspections during the pilot program and transition to routine, risk-based program
The TGA Good Clinical Practice Inspection Program (GCPIP) was developed through pilot inspections of investigator sites who volunteered for inspection. The pilot program confirmed the feasibility of an ongoing risk-based inspection program, which was endorsed for implementation by the Minister for Health.
Multiple sites volunteered for inspection even after completion of the pilot program. The TGA continued voluntary inspections during the transition to the routine, risk-based program, which provided an opportunity for the TGA to train GCP inspectors.
No major or critical deficiencies were observed. Minor deficiencies were identified in the following categories:
- Protocol compliance
- Human subject protection
- Study drug
The deficiencies identified during the pilot were similar to those frequently identified by GCP inspection programs delivered by other regulators such as the United States Food and Drug Administration (FDA), United Kingdom Medicines and Healthcare Products Regulatory Agency (MHRA) and the European Medicines Agency (EMA).
The main difference between the voluntary and routine programs is the inspection scheduling process. Prioritisation of sites for routine inspection is based on an assessment of risk, as described in the Guidance for GCP inspection of clinical trial sites for investigational biologicals and medicinal products. In particular, we consider the risks associated with the investigational medicinal product and the trial conduct, design and methods.
The routine inspection process is closely based on the pilot program. Inspectors used learnings from early inspections to streamline the process and develop more efficient tools and methods.
Current scope of the program and vision ahead
A clinical trial sponsor is responsible for undertaking an audit while a regulatory authority such as the TGA undertakes an inspection.
By undertaking systematic and independent audits, sponsors can ensure they are in the best position for any subsequent inspection.
See the ICH Guideline for Good Clinical Practice for the full definitions of audits (sections 1.6 and 5.19) and inspections (section 1.29).
All Australian investigator sites involved in clinical trials of medicines and biologicals, which are regulated under the CTN and CTA schemes, are subject to the GCPIP.
This includes commercially sponsored trials as well as investigator-led or academic trials, and includes all phases (first in human, phase I through to IV) and stages of the trial (start-up, ongoing, completed).
The scope of the GCPIP currently excludes sites conducting clinical trials of medical devices.
An investigator site is a site conducting a clinical trial involving a medicine or biological, regulated under the CTN/CTA pathway, including all auxiliary locations.
If the site is spread across several locations supporting conduct of the clinical trial (such as pharmacy, radiology, pathology, laboratory, consulting rooms, satellite sites), these locations may be also inspected.
The exact location of inspection activities is discussed and confirmed with the site following an inspection announcement.
Any future proposals to expand the scope of the program would be subject to the usual stakeholder consultation processes.
If GCP inspectors identify any significant observations related to stakeholders who are out of scope for the program (such as trial sponsor, contract research organisation (CRO), vendor, manufacturer, human research ethics committee (HREC), research governance office (RGO) or other approving authority), relevant comments may be recorded in the TGA inspection report (under "Comments"). The site will be asked to communicate the comments to the relevant stakeholders.
Routine GCP inspections include review of legal and administrative aspects, organisational aspects, the informed consent process, trial participant data and management of the investigational medicinal product (IMP) used in the trial.
The scope of a 'for cause' inspection is usually similar to routine inspections, with deeper focus on a specific area of compliance, linked to the inspection trigger. In some circumstances, the scope may be narrowed down to one (or a few) compliance area(s), targeting the trigger for inspection.
Site-level documentation that is required to be maintained by a site falls within scope of the GCP inspection.
If required, inspectors may request additional documentation at the time of announcement of the inspection, including records routinely maintained by the sponsor, or other records. Examples include:
- Site monitoring visit reports
- List of protocol deviations
- List of serious adverse events
- Audit certificate
- Safety monitoring plan
- Risk management plan.
If the site does not have access to these documents, they may request them from the sponsor or CRO.
The inspectors have relevant medical or scientific experience including a combination of clinical practice, monitoring, auditing, and regulatory inspections.
Yes, the inspectors will carry identification.
The number of inspectors attending will depend on the goal of inspection and complexity of the study and site.
In addition to inspectors, the TGA may be also represented by trainees, observers, and subject matter experts.
The inspectors will aim to meet all site and study requirements for direct access to the systems. Any potential administrative issues will be addressed on a case-by-case basis. The inspectors will meet all requirements for onsite visits (vaccination status check, health questionnaires etc as per site's policy).
The inspectors will take the management of unblinded data into consideration for studies that need to maintain a site’s blind (i.e. for studies that have not been unblinded) on a case-by-case basis.
The GCPIP commences in Q3 2022.
We prefer onsite inspections, but we do have the capacity to perform remote inspections. These may be considered in exceptional circumstances when travel or public health restriction measures will prevent the inspectors from accessing sites.
In some cases, depending on the nature of the information, reports about certain types of misconduct that are reported to the Australian Securities and Investments Commission (ASIC) may be entitled to the benefit of whistleblower protections under the Corporations Act 2001. Please see the following link for further information: Whistleblower rights and protections | ASIC - Australian Securities and Investments Commission.
International regulators deliver GCP inspection programs in line with their legislation. The objectives of these inspections may differ from the TGA’s objectives. While we will aim to avoid duplicating inspections conducted as part of another country’s inspection program, we may still select an Australian site conducting a study inspected by international regulators.
There is currently no intention to conduct site inspection as a requirement before approving new products.
In the initial stage of the program, the TGA aims to conduct 10 to 15 inspections per year.
A TGA GCP inspection can occur at any stage. We anticipate inspecting ongoing or recently completed studies in order to assess recent site practices.
We do not charge fees for inspections. The TGA does not reimburse investigator sites for their time dedicated to inspection preparation or attendance.
The investigator's responsibility to allow GCP inspections is defined in ICH GCP E6R2 section 4.1.4.
Sites selected for an inspection will be notified approximately 4 weeks prior to the planned inspection month and will be invited to suggest the most suitable date for the inspection within the selected month.
The announcement letter is sent to the Principal Investigator (PI) email address, listed in the CTN/CTA. It is the site's responsibility to ensure the clinical trial sponsor is aware of the current contact details of the PI at all times. The sponsor is responsible for ensuring these details are current in the CTN/CTA. The PI may share the inspection announcement letter with the sponsor, approving HREC, approving authority and other stakeholders are per site standard procedures.
Announced inspections will form the majority of our routine, risk-based GCP inspections. The notification letter will be distributed approximately four weeks before the planned inspection month. Following the announcement, we will work with the site to select a date that works for all parties involved.
Unannounced inspections are triggered by a specific cause, such as intelligence, and can be conducted without the usual prior notice. The sites will be notified usually within hour(s) of the inspection opening meeting. Such inspections are expected to be rare.
Sites will be informed of the inspection type (routine or 'for cause inspection) via the inspection announcement letter. Routine inspections are scheduled based on the factors outlined in the Guidance for GCP inspection of clinical trial sites for investigational biologicals and medicinal products.
In the case of a 'for cause' inspection, the reason for inspection will be included in the announcement letter.
For an unannounced inspection, the reason for inspection will be communicated during the inspection opening meeting.
The site should follow their own SOP in inspection readiness. The National Standard Operating Procedures for Clinical Trials, including Teletrials, in Australia also provides relevant guidance.
Preparation for a remote inspection is similar to preparation for an onsite inspection. The main difference will be in the conduct of the inspection, as requested documents will have to be accessed remotely and a facility tour may be done through videoconferencing.
If your site is selected for inspection, an inspection plan will be communicated to your site ahead of the inspection dates.
Under regulation 12AC, we can also inspect, examine, take measurements of, or conduct tests on (including by the taking of samples), anything on the site that relates to the trial; and take photographs, make video recordings, or make sketches of the site or anything on the site.
If a copy of the source record is required to support an observation, we will aim to take copies of de-identified records. Exceptional circumstances (when a copy of identifiable source record is required) will be addressed on a case-by-case basis.
Under most circumstances, the inspection report will be issued to the investigator site only, including the PI and site personnel authorised by them. It is expected that the site will share the report with other stakeholders, as appropriate.
During inspection there will be an optional daily debrief at the end of the day to clarify any observations. Alternatively, the closeout record (that documents the Corrective and Preventative Action (CAPA) plan) can also be utilised to clarify any disagreements.
The template for the CAPA plan in the form of a close out record will be provided when the inspection report is issued. The inspected site will use the close out record to provide details of the CAPA plan.
For critical and major deficiencies, the site representative will need to keep the TGA updated on the CAPA implementation status until the deficiency is considered closed by both parties. For minor deficiencies, the site is responsible for formulating a CAPA plan to be reviewed and accepted by the GCP inspector.
The TGA intends to publish de-identified information on completed GCP inspections on the TGA webpage in an annual metrics report. The de-identified inspection information may include:
- the number and type of inspections conducted in the previous 12 months
- aggregated information on critical, major, and minor deficiencies and whether they have been resolved
If the inspection leads to regulatory actions being taken under the Act, this information will be published in line with the TGA's compliance and enforcement procedures.
The TGA does not define the role of the inspected study's Approving Authority/Institution during an inspection as the program focuses on investigational sites. However, the PI can choose to invite a representative of the Approving Authority/Institution to the inspection.
While the TGA GCPIP does not inspect trial sponsors, it is important to note that as per ICH GCP E6R2, the trial monitor/ clinical research associate (CRA) plays a vital role in supporting the site to maintain inspection readiness throughout all stages of the trial.
The TGA does not define the role of the inspected study's sponsor during an inspection as the program focuses on investigational sites. However, the PI can choose to invite a representative of the sponsor to the inspection.
The TGA will communicate directly with the PI at the site. The PI is responsible for sharing relevant information with other stakeholders i.e. the trial sponsor, CRO, approving authority and HREC (as required). The clinical trial site/PI is expected to notify the trial sponsor that they have been selected for a TGA GCP inspection and agree on the level of sponsor support (if any) during the inspection. It is up to the PI’s discretion to share the inspection report and the corresponding CAPA with other relevant parties.
Note: The TGA is relying on the PI's contact information provided on the CTN/CTA application.
The process for the TGA GCPIP has been modelled on those published by the EMA. The inspections will verify site compliance with ICH GCP E6 R2 adopted by the TGA, as well as Australian legislation as set out in the Therapeutic Goods Act and Therapeutic Goods Regulations.
The TGA does not plan to conduct joint regulatory inspections with other regulators at this stage but the TGA inspectors may act as observers of foreign regulatory inspections of Australian sites.
If we identify significant deficiencies where the site has failed to comply with GCP requirements, we may share the inspection report with the approving authority and/or the approving HREC under the Therapeutic Goods (Clinical Trial Inspections) Specification 2020 (No.2).
The circumstances under which the TGA can take action to stop a trial are detailed in the Australian clinical trial handbook. Under paragraph (e) of item 3 in column 3 of Schedule 5A of the Therapeutic Goods Regulations a trial conducted under the CTN can be stopped. Under s 33(1) of the Acts Interpretation Act 1901 (Cth) an approval of a trial under the CTA can be revoked.
The TGA does not plan to publish any identified data on inspection outcomes, except in accordance with our compliance and enforcement procedures. For more information on the TGA’s approach to compliance, please visit Compliance management.
During the inspection, there will be an opportunity to discuss potential cases of noncompliance and provide guidance where appropriate and relevant.
Post-inspection, the review of the CAPA is anticipated to include information on how to correct and maintain compliance.
The slides used for the webinar are accessible here: Webinar presentation: Information on the TGA Good Clinical Practice (GCP) Inspection Program. Any updates to the guidance document will be available via the TGA website. Inspection-related questions can be directed to: GCP.Inspection@health.gov.au.