The regulatory environment

Clinical trials conducted using ‘unapproved therapeutic goods’ in Australia – that is, goods that have not been evaluated by the Therapeutics Goods Administration (TGA) for quality, safety and efficacy and entered into the Australian Register of Therapeutic Goods (ARTG) for general marketing – are required to make use of the Clinical Trial Notification (CTN) or Clinical Trial Exemption (CTX) schemes. This is because such products are considered experimental and do not have general marketing approval. Such goods include, but are not limited to, pharmaceutical substances and medical devices. There are a number of avenues in Therapeutic Goods Legislation (the Therapeutic Goods Act 1989, the Therapeutic Goods Regulations 1990 and the Therapeutic Goods (Medical Devices) Regulations 2002) via which ‘unapproved’ goods may lawfully be supplied. The CTN and CTX schemes provide two of these avenues for supply.

Under the CTN scheme, scientific and ethical review is provided by a human research ethics committee (HREC), with subsequent notification to the TGA. In the CTX scheme, the TGA has a direct role in the review of trial scientific data and must give an ‘approval’ for the proposed trial programme to go ahead; however, HREC review is still required. For comprehensive information regarding the CTN and CTX schemes, the document entitled Access to unapproved therapeutic goods should be consulted

It should be noted that, particularly in the case of prescription medicines, the definition of an unapproved good can encompass many aspects of a product. These include formulation, dose form, name, indications, directions for use and container. Therefore, even when a product is entered onto the ARTG, the product intended for use in a clinical trial may still be subject to the CTN or CTX scheme in order to be lawfully supplied. For example, the indication specified in the trial may be quite different than that for which the product is approved, the dosage may be higher than that approved for marketing, or the product may be sourced from a foreign market. It is also important to remember that there is a requirement that all therapeutic goods used in an unapproved fashion in a clinical trial, not simply the main product of interest, are noted on the CTN forms or in CTX documentation.

Clinical trials that do not make use of unapproved goods are not required to undergo either the CTN or CTX process, as these schemes exist to bestow an exemption on the clinical trial product(s) concerned such that their supply in Australia in the context of a clinical trial is lawful. As a consequence, trials comparing different surgical or therapeutic methods or trials that use Australian registered products within their marketing approval (e.g. long-term safety studies) do not require such an exemption.

However, ALL proposals to conduct clinical trials in Australia do require ethical review and approval by a HREC. A HREC must have notified its existence to the Australian Health Ethics Committee (AHEC) of the National Health and Medical Research Council (NHMRC) and provided assurances that it is operating within NHMRC guidelines. HRECs in Australia (with the assistance of sub-committees) generally provide both an ethical and scientific review, which may be supplemented on an as-needed basis by external expert advice as the committee(s) concerned sees fit. Applications to a HREC for approval of a research project are usually made using a standardised form that includes a number of essential elements.

From: The Australian Clinical Trial Handbook: A simple, practical guide to the conduct of clinical trials to international standards of Good Clinical Practice (GCP) in the Australian context.