Guidance on conducting clinical trials in Australia using 'unapproved' therapeutic goods

On March 15, 2018, the Therapeutic Goods Administration (TGA) of Australia released revised (version 2.0) of the Australian Clinical Trial Handbook. This handbook provides guidance on the legislative, regulatory and good clinical practice (GCP) requirements when conducting clinical trials in Australia using 'unapproved' therapeutic goods40. This revision, the first major change to the document since its inception in 2006, aims to bring the information in line with the current regulatory environment and to reflect current practices and meet government accessibility requirements.

The revised version 2.0 of the guidance covers all aspects of clinical trials, from different phases to Australia-specific aspects, for getting a study approved. The guidance aims to help sponsors, ethics committees, investigators and other groups understand their roles and obligations. New sections in the document include information on the advertising of experimental drugs and the retrieval and destruction of unapproved medicines. Other sections, such as a discussion of the merits of running trial extensions, are covered in more detail than in the earlier version.

This handbook assists trial sponsors, Human Research Ethics Committees (HRECs), investigators and approving authorities (institutions) to understand their roles and responsibilities under the therapeutic goods legislation.

This is a 55-page document guiding trial sponsors and principal investigators, Human Research Ethics Committees (HRECs), and approving authorities (institutions in which the trial is being conducted) on unapproved therapeutic goods, covering medicines, medical devices and in vitro diagnostics, biologics and other types of products.

Clinical trials involving therapeutic goods

According to the handbook, clinical trials involving therapeutic goods are generally undertaken to assess the effects, efficacy, performance and/or safety of the product. It is therefore necessary that clinical trials are conducted using appropriate exper al, all parties should be satisfied that the rights, safety and well-being of trial participants will be protected and that clinical trial data generated will be reliable and robust. To achieve such objectives, clinical trials involving 'unapproved' therapeutic goods must be conducted in accordance with:

  • The requirements of the Therapeutic Goods Legislation
  • The principles that have their origin in the World Medical Association Declaration of Helsinki
  • The National Statement on Ethical Conduct in Human Research (the National Statement) as in force from time to time
  • The relevant Good Clinical Practice (GCP) guideline
  • Other relevant requirements of Commonwealth and/or state and territory legislation
  • Site specific requirements

Determining the type of therapeutic good

The handbook describes the regulation of three main types of therapeutic goods:

  1. Medicines (including prescription medicines, over-the-counter medicines and complementary medicines)
  2. Medical devices (including in vitro diagnostic medical devices (IVDs))
  3. Biologicals (including human cell and tissue-based therapeutic goods, or live animal cells, tissues and organs)

The agency also regulates a very limited fourth type of goods known as other therapeutic goods (OTGs) examples of which include sterilants, disinfectants and tampons.

Figure 1: Four types of therapeutics goods regulated by the TGA

Determining if the product is 'unapproved'

According to the Australia Regulations, Therapeutic goods must be included in the Australian Register of Therapeutic Goods (ARTG) before they can be lawfully imported into, exported from or supplied in Australia unless otherwise subject to an exemption, approval or authority under the Therapeutic Goods Act 198941. In this new clinical trial handbook, the reference to 'unapproved' therapeutic goods is an abbreviated expression which is intended to include:

  • Any medicine not included in the ARTG, such as any new formulation, strength or size, dosage form, name, indications, directions for use or type of container of a medicine already in the ARTG
  • Any medical device (including an in vitro diagnostic device (IVD)) not included in the ARTG, such as any new sponsor, manufacturer, device nomenclature system code, classification or unique product identifier (for certain classes of medical devices only) of a medical device already in the ARTG

    • Any in-house IVD medical device, used for the purpose of a clinical trial, where the laboratory providing the in-house IVD is unable to comply with the regulatory requirements for in-house IVDs (a laboratory developed test used for research purposes where results of such testing are not being not being used in patient diagnosis, treatment or management decisions would not be considered an in-house IVD)
  • Any biological not included in the ARTG such as:

    • Any new applicable standards, intended clinical use or principal manufacturer of a Class 1 or 2 biological already in the ARTG
    • Any new product name, dosage form, formulation or composition, therapeutic indication, type of container or principal manufacturer of a Class 3 or 4 biological already in the ARTG
  • Therapeutic goods already included in the ARTG to be used in a manner not covered by the existing entry in the ARTG.

CTN and CTX Scheme

This handbook describes the two schemes under which clinical trials involving 'unapproved' therapeutic goods may be conducted in Australia:

  1. Clinical Trial Notification (CTN) scheme
  2. Clinical Trial Exemption (CTX) scheme

The CTN and CTX schemes aim to provide considerable benefits by providing the momentum to research and develop new therapeutic goods locally and facilitate early patient access to new therapeutic developments42. The main difference between the CTN and CTX schemes is agency's level of involvement in reviewing data about the therapeutic goods before the clinical trial commences.

Clinical trials that do not involve the use of 'unapproved' therapeutic goods are not subject to the requirements of the CTN and CTX schemes.

Role of trial sponsors

According to the handbook, all clinical trials conducted in Australia must have a trial sponsor who is an Australian entity (an overseas company cannot be the sponsor of a trial in Australia). Sponsors of trials under the CTN or CTX schemes may include individuals, companies, institutions, or organizations. The trial sponsor is responsible for the initiation, management and financing (or arranging finance) of the trial and carries the medico-legal responsibility associated with its conduct. The Australian trial sponsor is the entity responsible for submitting a CTN or CTX to the agency.

The handbook also defines detailed roles of other stakeholders like:

  1. Role of Human Research Ethics Committees (HRECs)
  2. Role of approving authorities
  3. Role of principal investigators
  4. Role of TGA, the agency

Safety Reporting to the Agency

The handbook lays down the timeframes for reporting of Safety Information from the clinical trials:

  • For Single case events from Australian sites;
  • Significant safety issues and overseas regulatory action; and
  • Other Report Types

Advertising 'unapproved' therapeutic goods

The handbook says that it is an offence to advertise any therapeutic good that has not been included in the ARTG under the Therapeutic Goods Act, 1989. While the trial sponsor can promote their trial in the public domain, they cannot specifically mention the name of the therapeutic good being used in the trial. Further, any advertisement for a clinical trial should be approved by the Human Research Ethics Committees (HREC) reviewing the trial.


TGA's revised clinical trial handbook provides guidance on the legislative, regulatory and good clinical practice (GCP) requirements when conducting clinical trials in Australia using 'unapproved' therapeutic goods. The revisions, which are the first major changes to the document since 2006, bring the information in line with the current regulatory environment and provide further details about how to set up and run clinical trials in Australia.





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