By Associate Professor Peter Keller, Senior Manager, Research Integrity
Almost 16 years after the Australian Government’s response to the recommendations of the Review of Clinical Trials and Access to Unapproved Therapeutic Goods (the Bansemer Report)¹, and following a successful pilot program of voluntary Good Clinical Practice (GCP) inspections, the Therapeutic Goods Administration (TGA) published on 12 May 2022 guidance on the implementation of an ongoing risk-based GCP Inspection Program.²
‘The Guidance for GCP inspection of clinical trial sites for investigational biologicals and medicinal products (version 1.0, April 2022)’ covers the background to and legislative basis for GCP inspections in Australia. It outlines the key responsibilities attributable to trial sponsors, Human Research Ethics Committees (HRECs), approving authorities (institutions) and Principle Investigators (PIs) under the legislative framework, in harmonisation with international inspection programs and approaches.
As with comparable regulatory agencies, the TGA will select a small percentage (between 1 and 3%) of regulated (Clinical Trial Notification or Clinical Trial Approval) trials for inspection each year. Importantly, the inspection program shifts the chance of any one trial site being routinely inspected by the TGA from zero to about 4% (based on the number of unique trial sites in Australia), with the expectation that this will drive behaviour across the sector and improve compliance with the applicable GCP guideline.
The inspection program has been deliberately limited in scope to investigator sites rather than other sites involved in clinical trials, noting the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) inspect other types of sites, ie, trial sponsors, contract research organisations and HRECs, and trials involving therapeutic goods regulated as biologicals or medicinal products, and not medical devices.
It is worth noting that the Therapeutic Goods Regulations (1990) (‘the Regulations’) were amended in late 2019 to clarify that the inspection and compliance powers in the Regulations applied to notified (CTN) and not just approved clinical trials (CTA). A similar amendment to the Therapeutic Goods (Medical Devices) Regulations (2002) would be required prior to the expansion in scope of the inspection program to include medical device clinical investigations.
The TGA guidance describes the inspection process covering various topics, including prioritisation and scheduling of GCP inspections, the kinds of inspections TGA might conduct, the inspection process, and how TGA will report and follow up on an inspection.
The majority of GCP inspections are anticipated to be routine rather than ‘for cause’, and announced rather than unannounced or at short notice. Organisations can expect, in most cases, four weeks’ advance notice of an inspection. An inspection could be conducted onsite, remotely or using a hybrid model, but as acknowledged in the International Coalition of Medicines Regulatory Authorities’ (ICMRA) ‘Reflections on the regulatory experience of remote approaches to GCP and GMP regulatory oversight during the COVID-19 Pandemic’,³ “there are limitations and challenges associated with the use of remote inspections, assessments and evaluations, and the full extent of their use in normal circumstances remains to be defined”. So one should expect most GCP inspections to be conducted onsite.
The TGA’s GCP inspection program has been developed to align with internationally harmonised processes and modelled on those published by the European Medicines Agency (EMA) to cover five key aspects of trial conduct:
1. Legal and administrative – HREC, Governance approvals and regulatory notification.
2. Organisational – qualifications and experience of site personnel, delegation of authority, standard operating procedures (SOPs), facilities and equipment, monitoring records.
3. Informed consent.
4. Trial participant data.
5. Management of investigational medicinal product (IMP).
The guidance document is written with investigator site PIs as the target audience and includes basic guidance regarding how to prepare for an inspection, including notification to the institution (eg, the Research Governance Office), the trial sponsor (as required under the clinical trial research agreements for commercially sponsored trials), the clinical trial team and ensuring access to clinical trial records and source documents.
Implementation of the National Clinical Trials Governance Framework4, as recently endorsed by all Australian jurisdictions in February 2022, brings into focus the requirement that systems and processes should be in place to implement effective clinical trials governance considering local needs, values and the context in which services are provided. When combined with the TGA’s endorsement of the National Standard Operating Procedures for Clinical Trials5, it becomes clear that the key concept is quality, and the processes and systems in support of that.
The increased focus on quality is also evident in the change in wording from ICH E6 (R2) and the addition of principle 7 in ICH E6(R3) — “Quality should be built into the scientific and operational design and conduct of clinical trials” — which shifts the focus to building quality into the design of clinical trials from the very beginning. This requires a change in thinking from Trial Master File (TMF) to Quality Management System (QMS).
How can Chrysalis help?
The team at Chrysalis is made up of clinical research professionals with decades of experience and unique expertise, including direct experience developing and implementing the TGA’s GCP inspection program and running on-site trials. Chrysalis is your expert partner when it comes to Research Governance, Research Integrity, Quality Management Systems and implementation of the National Clinical Trials Governance Framework.
To discuss how we can partner with you, and ensure you are inspection ready, please contact our team at firstname.lastname@example.org or call 1300 287 173.