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Australian clinical trial handbook
Guidance on conducting clinical trials in Australia using 'unapproved' therapeutic goods
Clinical trials involving therapeutic goods
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 experimental designs to obtain valid data without exposing participants to unnecessary risks.
Before starting a clinical trial, 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
See the Clinical Trials Toolkit on the Australian Clinical Trials website for further information and useful resources.
Before conducting a clinical trial in Australia, the trial sponsor will need to consult a HREC to determine whether an exemption under the CTN scheme or approval under the CTX scheme is required for the trial.
Clinical trials that do not involve the use of 'unapproved' therapeutic goods (including placebos) are not subject to CTN or CTX requirements. However, all clinical trials require HREC approval before the clinical trial may commence.
The trial sponsor will need to determine the following for each product used in the clinical trial:
- is the product a therapeutic good (and therefore regulated as a therapeutic good)
- the type of therapeutic good (and therefore regulated as a medicine, medical device or biological)
- if the product is considered 'unapproved' (and therefore a CTN or CTX submission is required)
Is the product a therapeutic good?
The trial sponsor must first determine whether any of the products to be used in a clinical trial meet the definition of a therapeutic good and are regulated under the therapeutic goods legislation.
The following guidance may assist trial sponsors to determine if a product is a therapeutic good:
- What are 'therapeutic goods'? provides definitions and examples of therapeutic goods
- Is my product a therapeutic good? is an online tool designed to assist in determining whether a product is a therapeutic good, and if so, the type of therapeutic good (although this is not specifically designed for clinical trials)
- Food and medicine regulation and the Food-Medicine Interface Guidance Tool may assist in identifying whether a product is regulated as a medicine or a food
Section 3 of the Therapeutic Goods Act 1989 provides definitions for therapeutic goods and therapeutic use. Although the term 'therapeutic use' is sometimes used in connection with phase IV clinical trials for medicines and biologicals, for the purposes of the CTN and CTX schemes, the use of a medicine or biological in a phase I, II or III clinical trial will also generally be considered to be for therapeutic use. A medicine, biological or medical device that is the subject of a clinical trial will generally be considered to be a therapeutic good regardless of the phase or stage of the trial.
Determine the type of therapeutic good
The trial sponsor needs to correctly identify the type(s) of therapeutic good(s) being supplied in a clinical trial as different regulatory requirements apply.
This handbook describes the regulation of three main types of therapeutic goods:
- medicines (including prescription medicines, over-the-counter medicines and complementary medicines)
- medical devices (including in vitro diagnostic medical devices (IVDs))
- biologicals (including human cell and tissue-based therapeutic goods, or live animal cells, tissues and organs)
See Products regulated as biologicals for information on therapeutic goods that are regulated as biologicals. Biological prescription medicines (for example, vaccines that do not contain human cells, plasma derivatives, recombinant products) are not regulated by us as biologicals. They are regulated as medicines.
We also regulate a fourth, very limited, type of goods known as other therapeutic goods (OTGs). These include sterilants, disinfectants and tampons.
Use of the term 'investigational' in this handbook is explained below:
- investigational product - any therapeutic good (including placebos) being tested or used as reference in a clinical trial
- investigational medicinal product - an investigational product that is a medicine
- investigational biological - an investigational product that is a biological
- investigational medical device - a medical device being assessed for safety or performance in a clinical investigation
Types of therapeutic goods
Four types of therapeutic goods:
Products that act by pharmacological, chemical, immunological or metabolic means in or on the body of a human (includes biological medicines, e.g. monoclonal antibodies, vaccines that do not contain human cells, plasma derivatives, and recombinant products)
- Medical device
Any instrument, apparatus, appliance, material or other article intended to be used for human beings for the purpose of one or more of the following:
- diagnosis, prevention, monitoring, treatment or alleviation of disease
- diagnosis, monitoring, treatment, alleviation of or compensation for an injury or handicap
- investigation, replacement or modification of the anatomy or of a physiological process
- control of conception
and that does not achieve its principal intended action in or on the human body by pharmacological, immunological or metabolic means, but that may be assisted in its function by such means
or is an accessory to such an instrument, apparatus, appliance, material or other article
Product made from or that contains, human cells or human tissues, or live animal cells, tissues or organs and that is used to:
- treat or prevent disease, ailment, defect or injury
- diagnose a condition of a person
- alter the physiological processes of a person
- test the susceptibility of a person to disease
- replace or modify a person's body parts
(unless excluded or regulated as therapeutic goods, but not as biologicals)
- Other therapeutic good
A product that is not regulated specifically as a medicine, biological or medical device (includes sterilants, disinfectants and tampons)
Refer to the Therapeutic Goods Act 1989 for the complete definitions.
Determine if the product is 'unapproved'
Therapeutic goods must be included in the Australian Register of Therapeutic Goods (ARTG) before those goods can be lawfully imported into, exported from or supplied in Australia unless otherwise the subject of an exemption, approval or authority under the Therapeutic Goods Act 1989.
The therapeutic goods legislation provides a number of avenues to allow access to therapeutic goods that are not included in the ARTG. The CTN and CTX schemes provide for the lawful importation into and/or supply in Australia of 'unapproved' therapeutic goods for use solely for experimental purposes in humans.
For the purposes of this 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 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
The overall decision as to whether a CTN or CTX is required in relation to the use of the therapeutic goods is the responsibility of the trial sponsor. Consultation with the HREC that will approve the trial protocol may assist in the decision.
When a product is included in the ARTG, the entry applies to a particular sponsor (i.e. the individual or company intending to supply the goods). If a same or similar product is imported by another company or individual it is considered 'unapproved'.
Trial sponsors who are considering supplying an 'unapproved' therapeutic good, need to recognise that it has not been evaluated by us for quality, safety, efficacy or performance.
Other pathways for accessing 'unapproved' therapeutic goods
The CTN and CTX schemes are not intended to be used as a means for obtaining access to 'unapproved' therapeutic goods for an individual patient. There are other mechanisms for lawfully supplying 'unapproved' therapeutic goods to individual patients outside clinical trials. Those mechanisms are:
Equally, the above pathways should not be used by health practitioners for the purposes of conducting a clinical trial. Health practitioners wanting to conduct a clinical trial (investigator-initiated trials) using an 'unapproved' therapeutic good, should do so using the CTN or CTX pathways, as appropriate.
The regulatory controls placed on clinical trials conducted through the CTN and CTX pathways provide sufficient assurance that high quality, credible data that contribute to the answering of specific scientific questions is collected, while also protecting the rights, safety and well-being of clinical trial participants.
Certain 'unapproved' therapeutic goods used in clinical trials
All 'unapproved' therapeutic goods, not just the investigational product(s), must be the subject of an exemption, approval or authority under the Therapeutic Goods Act 1989 to be lawfully supplied in a clinical trial.
There is no entry for 'placebo' in the ARTG. Therefore, a placebo is considered to be an 'unapproved' therapeutic good and a CTN or CTX must be in place before a placebo can be supplied for use in a clinical trial. This is the case even if the investigational product(s) are already included in the ARTG.
A comparator is an investigational or marketed product, or placebo, used as a reference in a clinical trial. If the trial sponsor determines a comparator to be an 'unapproved' therapeutic good, then a CTN or CTX must be in place before the product can be supplied for use in a clinical trial. This includes comparators that are included in the ARTG and altered for the purposes of a trial.
Medical software and mobile medical 'apps'
Medical software and mobile medical 'apps' used in clinical trials may be regulated as medical devices and therefore may require exemption under the CTN scheme or approval under the CTX scheme. Further information can be found at Regulation of medical software and mobile medical 'apps'.
Laboratory kits and procedure packs
If a laboratory kit or procedure pack (including any component or in its entirety) is determined by the trial sponsor to be an 'unapproved' medical device, then an exemption, approval or authority must be in place for the goods to be supplied (this includes the CTN and CTX schemes).
It is the trial sponsor's decision based upon the advice from the approving HREC, on how to notify a procedure pack on the CTN form.
Non-investigational products used in clinical trials
Annex 13 of The Pharmaceutical Inspection Convention and Pharmaceutical Inspection Cooperation Scheme (jointly known as the PIC/S) Guide to Good Manufacturing Practice for Medicinal Products describes products other than the test product, placebo or comparator that may be supplied to participants in a trial. Such products may be used as support medication for preventative, diagnostic or therapeutic reasons or needed to ensure that adequate medical care is provided for the participant (for example, an antiemetic supplied in a chemotherapy trial). If the trial sponsor determines such a product to be an 'unapproved' therapeutic good, then an exemption, approval or authority must be in place for the goods to be supplied (this includes the CTN and CTX schemes).
Genetically Modified Organisms (GMO)
Some therapeutic products may involve the use of a Genetically Modified Organism (GMO). Trials involving GMOs are subject to the Gene Technology Act 2000 and Gene Technology Regulations 2001, and corresponding state and territory legislation.
A trial sponsor proposing to use a GMO must apply to the Office of the Gene Technology Regulator (OGTR) for a licence or exemption documentation and this must be provided to the local Institutional Biosafety Committee at the clinical trial site. OGTR has published guidance for clinical trials involving GMOs at Requirements under the Gene Technology Act 2000 for clinical trials in humans involving GMOs - Guidance for clinical trial sponsors.
- The use of the expression 'unapproved' in this handbook refers to the international expression 'approval for general marketing'. It does not refer to the absence of any express statutory approval under the therapeutic goods legislation, but rather the absence of any registration, listing or inclusion of the therapeutic goods in the ARTG.