2. General Questions

2.1 Name of Regulatory Authority

Medicines and Medical Devices are regulated in Australia by the Therapeutic Goods Administration (TGA). 

https://www.tga.gov.au/

The TGA is a Commonwealth government department that sits under the federal government Department of Health.

Street Address (for deliveries):
136 Narrabundah Lane
Symonston ACT 2609
Australia

For clinical trial inquiries:

Phone: 1 800 020 653 (free call within Australia), +61 2 6289 4614, or +61 2 6232 8106
Fax: +61 2 6232 8112
E-mail: clinical.trials@health.gov.au

2.2 Name of Ethics Committee

Australia has a decentralized process for the ethics review and approval of clinical trial research which places the responsibility for ethics approval at an institutional level. Institutional-level ethics committees are referred to in Australia as Human Research Ethics Committees (HRECs). This is defined within the National Statement on Ethical Conduct in Human Research (2023) (effective 1 January 2024). 

National Statement on Ethical Conduct in Human Research 2023

Each of the Australian states and territories has separate legislation relevant to the conduct of clinical trials. Investigators, HRECs, approving authorities, and trial sponsors should ensure that they comply with the specific requirements for each jurisdiction.

Institutions are responsible for establishing procedures for the ethical review of human research, which can take place at different levels depending on the level of risk. Research with more than a low level of risk must be reviewed by an HREC. In addition to ethics approval, sites where clinical trials are conducted must also authorize the research for their site.

Section 5 of the National Statement on Ethical Conduct in Human Research 2023 states the following in relation to Research Governance:

5.1.1.   Each institution must develop and adhere to a set of policies grounded in accepted ethical principles and principles of research integrity as set out in the National Statement and the Australian Code for the Responsible Conduct of Research.

5.1.2    Each institution must ensure that any human research for which it is responsible is designed, reviewed, approved, authorized, conducted, and monitored in accordance with the National Statement and the Code and any policies that they have developed that form part of their research governance framework.

5.1.3    Each institution should be satisfied that the human research for which it is responsible meets both relevant ethical standards and scholarly or scientific standards. 

5.1.4    Each institution should be satisfied that the human research for which it is responsible adequately takes account of consumer and community perspectives, with reference, where relevant, to NHMRC’s Statement on Consumer and Community Involvement in Health and Medical Research. 

5.1.5    Institutions should publish (such as on their website) clear policies and procedures for ethics review and approval and institutional authorization of research. 

5.1.6    Where ethics review is required, approval must be obtained prior to the commencement of the research. Retrospective ethics approval of research is not supported by the National Statement. 

 5.1.7    Institutions should have a clearly defined decision-making process for determining whether an activity is research or if it is another activity, such as quality assurance, and have separate mechanisms for the review and authorization of each. These mechanisms should be set out in the institution’s policies and procedures. (See Ethical considerations in quality assurance and evaluation activities).

2.3 Clinical Trial Application Language

English

2.4 Is regulatory approval required from both regulatory authorities and/or EC?

It depends on the product type. For biologicals and high-risk products, full regulatory approval (meaning approval from both EC and RA) is required prior to the commencement of the trial (including review and approval of a clinical trial application (CTA) by TGA). For other products, an ethics review is required and the regulatory authority only needs to be notified of the study prior to its commencement (CTN – clinical trial notification). 

2.5 Can regulatory authority and EC submission be done in parallel?

Yes.

2.6 Requirement of any import permit/license before investigational product/study product is shipped from point of origin

Yes. Sponsors must submit an application to TGA to request the import of unapproved medicines for use in a clinical study.

Submit an application

2.7 Biological Specimen Export Requirements

Sponsors must obtain an export permit from TGA to export human body fluids, organs, and other tissues. A permit is not required if each individual container is 50 mL or less, but substances derived from human blood require a permit regardless of the volume.

The application form is provided at the link below: 

Export Permit Application

Permits can be applied for as: 

• Single-use – a one-time application to support one consignment to one destination.
• Annual permit – covering multiple consignments to one destination over a one-year period.

2.8 Are studies of GMOs permitted (e.g., GMOs used in vaccines/vaccine manufacture and other modified products)?

Yes. GMOs may be used subject to approval from both the TGA and the Office of the Gene Technology Regulator (OGTR).

The introduction of a GMO into a person via a medicine requires approval by the regulators, except where the GMO is a human somatic cell meeting the specific criteria, outlined below.

Genetically Modified Human Somatic Cells 

Introduction of GM human somatic cells, including re-introduction of GM autologous cells into the person from whom they were derived, does not require a license, provided that:

• the GM somatic cells cannot secrete or produce infectious agents as a result of the genetic modification; and
• if the GM somatic cells were modified using a viral vector, they have been tested for and found not to contain, other viruses likely to recombine with the genetically modified nucleic acid, and the viral vector is no longer present in the GM somatic cells.

Dealings with GM somatic cells that meet these requirements are classified as ‘exempt’. If the GM somatic cells do not meet the above criteria, then the clinical trial requires a license.

Types of GMO Licences

There are two types of license, authorizing either:

1. Dealings involving intentional release (DIR) into the environment; or
2. Dealings not involving intentional release (DNIR)

For clinical trials, the Regulator considers that intentional release into the environment occurs when the specific mode of administration results in the release of the GMO (e.g., administration using an intranasal spray or nebulizer, or when the GMO may be shed, excreted, or otherwise transmitted from trial participants to other people or animals over the course of the study). In these cases, a DIR license is generally required.

Clinical trials that are DIRs are usually licensed as ‘limited and controlled’ releases. To qualify as a limited and controlled release, the primary purpose of the work must be to conduct experiments and the application must propose appropriate limits on the release of the GMO and controls to restrict its dissemination or persistence in the environment.

Where it is not expected that the GMO will be released into the environment, a DNIR license is appropriate. Applications will need to include data that supports this conclusion. Note that the Regulator considers some adeno‐associated virus (AAV)-based gene therapy treatments as eligible for DNIR licensing. Please contact the OGTR for guidance if your application involves an AAV-based GMO.

When screening license applications, the OGTR will consider whether the application type is appropriate for the GMO and the proposed dealings. Assessment of an incorrectly categorized license application may be delayed while the OGTR seeks more information from the applicant.

Under the requirements of the Gene Technology Act 2002, the OGTR has issued guidance for conducting human clinical trials involving GMOs.

2.9 Is in-country sponsor presence/representation required?

Yes. Sponsors must be a local Australian legal entity. The role of the Sponsor is well defined within “The Australian Clinical Trial Handbook”.

2.10 Is there any mandatory requirement to identify a local PI or can a PI be based in a foreign country?

Yes. Whilst the Clinical Trial Handbook does not state specifically that the PI must be located in Australia, it clearly states that the PI is the person individually responsible for the site, and therefore by inference, the Principal Investigator must be located within Australia.

https://www.tga.gov.au/sites/default/files/australian-clinical-trial-handbook.pdf

2.11 Is there any mandatory requirement to identify a local chief or coordinating investigator?

There is no mandatory requirement for a local Chief. However, for multicentre studies, they are often used as follows:

Coordinating Principal Investigator (CPI)

In Australia, in the context of the National Mutual Acceptance (NMA) scheme, this term is sometimes used to describe the health professional, whether or not they are an Investigator at any particular site, who is assigned the responsibility for the conduct of the study and coordination of Investigators at different sites participating in a multicenter trial. This includes coordination of all HREC processes, such as the initial submission and any required notifications throughout the trial, on behalf of the individual Primary and/or Satellite Site Investigators.

However, the CPI cannot be responsible for trial activity at a site (except where they are also the Principal Investigator).

2.12 If the applicant is CRO or a third party, does regulatory authority need any authorization or transfer of obligations from the sponsor? Is there any standard template available? Does the authorization letter need to be notarized and/or apostilled?

A transfer of obligations letter is preferable. There is no defined format for this document and there are no requirements for notarization/apostillation.

2.13 Is there a requirement to register clinical trials on a local registry or database?

Trials conducted in Australia must be registered on the Australian New Zealand Clinical Trials Registry.

ANZCTR is an online register of clinical trials being undertaken in Australia, New Zealand, and elsewhere. The ANZCTR includes trials from the full spectrum of therapeutic areas of pharmaceuticals, surgical procedures, preventive measures, lifestyle, devices, treatment and rehabilitation strategies, and complementary therapies.

In the above statement, elsewhere refers to clinical trials being run in other countries and recruiting within Australia. Please see the below statement regarding international clinical trials registering with ANZTR:

‘The ANZCTR encourages registrants to use their local Primary Registry if available. For a full list of Primary Registries please please go to www.who.int/ictrp/network/primary/en/. As the ANZCTR is funded by Australia and New Zealand, we must prioritize submissions from these countries first, followed by submissions from countries that do not have their own primary registries, and then finally submissions which are from countries that do have their own primary registry in the WHO Registry Network. Accordingly, if you are applying from outside Australia or New Zealand and have no recruitment sites in Australia or New Zealand, then there may be a delay in processing your submission. All submissions must be written in clear and concise English, otherwise, we have the right to reject them.’

2.14 What is the local requirement for clinical study documents archival; minimum of years for the archival, specific format followed (electronic/paper and/or both)?

For most clinical trials, research data must be retained for 15 years. For areas such as gene therapy, research data must be retained permanently (e.g. data in the form of patient records). 

The guidance does not define the specific format in which data must be retained. Typically, either electronic or paper format is acceptable as long as this is consistent with the study’s data management plan. 

2.15 Requirements around periodic safety reporting and timelines on SAEs/AEs/ADRs/SUSARs/DSURs.

Trial sponsors should refer to the NHMRC Guidance: Safety Monitoring and Reporting (NHMRC Guidance) for safety reporting requirements. The NHMRC guidance addresses the monitoring, collection, and reporting of adverse events that occur in clinical trials involving therapeutic goods conducted under the CTN or CTA schemes. The NHMRC Guidance has aligned with the European Union’s Clinical Trial Regulations: Regulation EU No 536/2014.

1. Single case events from Australian sites: SUSARS and USADEs

2. Significant safety issues* and overseas regulatory action 

*SSIs that arise from analysis of overseas reports (relating to a clinical trial in Australia) should be reported to us as per the timeframes above.

** We should receive notification that a SSI has occurred but the amendment revising trial documentation should be submitted to the HREC only.

Note: A SUSAR or USADE may also meet the definition of an SSI.

3. Other report types 

2.16 Requirement on any periodic clinical study update, specific template, and its frequency (e.g., interim, or annual progress report and final report, etc.)?

Reports every 6 months.

A sponsor of therapeutic goods in relation to an exemption under section 18, 32CA, or 41HA or approval under section 19, 32CK, or 41HB of the Therapeutic Goods Act 1989 must provide a report to TGA every six months. Regulation 47B of the Therapeutic Goods Regulations 1990 outlines the details required in such reports.

2.17 Do the country regulations allow a Decentralized Clinical Trial (DCT) model (e.g., eICF, ePROs administration, remote investigator site, etc.)? 

TGA does not have any specific guidance around Decentralized Trials. There is nothing preventing a DCT pending agreement by the HREC.

Teletrials (using a hybrid model) are now highly encouraged by the Health Departments of Federal and State Governments as a means of facilitating access to trials for patients in remote Australian locations. Most States have now implemented guidance on the conduct of teletrials and actively encourage this model.

Links to the State guidance on Teletrials are provided below:

2.18 Has a fully virtual trial (DCT) been conducted in the country yet? If so, please provide an example including the registration number and any link to it, whether COVID/non-COVID trials.

There is no definitive evidence to suggest that a fully decentralized trial has been conducted in Australia. However, hybrid studies have been conducted and there is increased acceptance of decentralized aspects of study design following the COVID-19 pandemic. 

An example of a hybrid study conducted in Australia is described in the attached publication:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9306873/#bcp15205-bib-0024

2.19 Are there any non-regulatory DCT initiatives in the country, such as where investigator sites and local CROs founded an alliance?

Yes. Medicines Australia has been involved in supporting the implementation of teletrials and has set up a series of tools to support the establishment of a teletrial.

Implementation of Teletrials

In June 2023, the Australian Association of Regulatory and Clinical Scientists (ARCS) released a White Paper on the use of consistent terminology for decentralized trials. 

2.20 Does the local regulation require notification of “serious breaches” of GCP or the trial protocol (that is a breach that is likely to affect to a significant degree either the safety or physical or mental integrity of the subjects of the trial; or the scientific value of the trial)?

The reporting of breaches is described in the following document from the NHMRC.

Sponsors have primary responsibility for determining whether any suspected breach meets the definition of a serious breach. In practice, this assessment is often conducted or overseen by the group tasked with monitoring the general quality of the trial and its adherence to the protocol. In particular, the judgment on whether a breach is likely to have a significant impact on the reliability and robustness of trial data should be made by the sponsor and depends on a variety of factors (e.g.: the design of the trial, the type and extent of the data affected by the breach, the overall contribution of the data to key analysis parameters, and the impact of excluding the data from the analysis). 

However, if the sponsor is unsure whether a potentially serious breach has a significant impact on the rights or safety of participants, they should contact the reviewing HREC for advice.

Sponsors should also:

1. Develop documented processes for managing serious breaches including:
   • The assessment of whether the serious breach is isolated or systemic;
   • The assessment of the impact of the serious breach on participants and on the reliability and robustness of trial data - the investigation procedure;
   • The reporting procedure - the management of corrective and preventative action (CAPA);
   • The circulation and retention of documents relating to serious breaches;
2. Report serious breaches to the reviewing HREC within 7 calendar days of confirming a serious breach has occurred and provide follow-up reports when required.
3. For serious breaches occurring at a trial site, notify the site’s principal investigator within 7 calendar days of confirming a serious breach has occurred.
4. Perform a root cause analysis and ensure that appropriate corrective and preventative actions are taken.
5. Where the sponsor determines a third-party report, provided to it by the HREC, meets the definition of a serious breach, report the serious breach to the reviewing HREC within 7 calendar days of this decision.
6. Where the sponsor determines a third-party report, provided to it by the HREC, does not meet the definition of a serious breach, notify the reviewing HREC by letter or e-mail, including a justification for this decision, within 7 calendar days of confirming a serious breach has not occurred.
7. Keep written records of all suspected and confirmed serious breaches, including the justification for determining that a suspected breach does not meet the definition of a serious breach.
8. Notify the TGA and the reviewing HREC if the serious breach leads to the closure of the site.
9. Report to the TGA any serious breach that involves a defective product that may have wider implications for the supply chain for that marketed product:
   • Commercial sponsors report to the TGA using existing product surveillance processes
   • Non-commercial sponsors (e.g. universities) may either report to the TGA directly or to the Marketing Authorization Holder/manufacturer (who would report to the TGA).

2.21 Does RA/CA require insurance and indemnity to cover the sponsor and investigator’s potential liability?

The TGA advises that it is the responsibility of the sponsor (that is, the individual who endorses the CTN or CTX form) of a clinical trial to:

• provide appropriate insurance and indemnity for the trial and trial-related staff, as well as measures for subject compensation for trial-related injury.

 This insurance should comprise of two different aspects as follows:

1. Indemnity and insurance arrangements that the entity has or puts in place to protect it against liabilities that it may incur or suffer in the course of its clinical trial activities. Where these take the form of insurance, the ‘insured’ will typically be the sponsoring entity, its directors and officers, and its employees. The considerations in this respect are not unique to clinical trials – such an entity will have various types of liability insurance in place to protect it against liabilities incurred in relation to its other activities.
2. The indemnity and insurance requirements imposed by a party conducting a clinical trial upon another party that is involved in that clinical trial in some capacity – for example, as a sponsor, collaborator, or contributor. The most common requirements are for the other party to provide a (contractual) indemnity to the first party and evidence of its insurance arrangements. The effect of such requirements is twofold:
   1. the indemnity given by the other party protects the first party against certain liabilities; and
   2. as the other party will have insurance covering its activities, the first party will be reasonably assured that the other party should be able to meet a liability that arises from its (negligent) conduct. (Indeed, if there is a requirement for the first party to be included as an insured on the other party’s insurance arrangements, then the first party will have a direct right to seek protection against the insurer.

Insurance requirements conducted under the Teletrial model:

All sites must have their own insurance. If indemnity is provided by the sponsor to the primary site, it must also include all satellite sites.

If indemnity isn’t provided by the sponsor, each site, including satellite sites, must have its own.