Australian Regulation on Clinical Trials
In Australia, the Therapeutic Goods Administration (TGA) is the authority that is responsible for approving clinical trials, oversight, and inspecting the therapeutic goods at the national level. According to the provisions of the Therapeutic Goods Act (TGAct) and the Therapeutic Goods Regulation (TGR), TGA is in charge of granting exemptions for the supply of therapeutic goods for used in clinical trials that are yet to be approved¹. The authority also standardises the use of these goods in trials especially experiments involving humans.
Generally, the Clinical Trial Notification (CTN) and the Clinical Trial Approval (CTA) schemes controls therapeutic goods set to be used in clinical trials. The two schemes are responsible for the assessment of the safety, quality, and usefulness of all therapeutic goods for clinical trials. This is because these goods which include pharmaceutical products and medical devices are usually considered experimental and do not have general marketing approval. The two schemes provide avenues for the lawful supply of these unapproved goods. These avenues are the Therapeutic Goods Act of 1989, the Therapeutic Goods regulation of 1990, and the Therapeutic Goods (medical devices) Regulation of 2002.
Under the CTN scheme, the individual sponsoring the clinical trial should notify the Therapeutic Goods Act authority of their intention to sponsor the trial. This grants the ethics committee and the institution the opportunity for examination and approval of the use of ‘unapproved’ therapeutic good. Before the commencement of the trial, the sponsor has to ensure that all applicable approvals have been made.
1. Tobey-Ann Pinder and Dilip Ghosh, “Complementary medicine regulation in Australia,” Nutraceutical and Functional Food Regulations in the United States and around the World, 2019, xx, doi:10.1016/b978-0-12-816467-9.00025-3.
The sponsor may submit the CTN to the TGA simultaneously with approval from the ethics committee and the institution.
In case of any insufficiencies or concerns, the TGA may ask for additional information from the sponsor regarding the CTN. For the unapproved goods to be supplied for use in the clinical trial, the sponsor must make sure that the TGA has been notified through the online CTN form. Additionally, the ethics committee and the institution should have approved the goods and the notification fee cleared. The TGA might provide some written information regarding the therapeutic goods give notice of in the CTN form².
During submission, any data that is related to the clinical trial is not evaluated. It is the responsibility of the Human Research Ethics Committee (HREC) to validate the design of the clinical trial. HREC further validates the balance between the risk associated with the trial versus the injury of the therapeutic good, whether the process is ethically acceptable, and finally is the approval of the process. HREC also monitors the way in which the trial is conducted.
CTN schemes application is done online through an online form. The TGA takes between 5 to 7 working days to process the application. Any information regarding the process is available through the online portal for printing and downloading. An approving authority is an body in which the trial is to be carried out. With advice from the HREC, the approving authority grants the final approval of the site for the trial. The sponsor is thus under an obligation to ensure all approvals have been made before supplying the unapproved therapeutic good.
2. Keith Potent, “The future of phage clinical trials in Australia,” Microbiology Australia 40, no. 1 (2019): xx, doi:10.1071/ma19004.
Under the CTA scheme, the sponsor of the clinical trial should submit an application to the TGA. This is done dfor the TGA to grant the sponsor approval to supply the unapproved goods. The sponsor pays an application fee to the TGA while submitting. The Therapeutic Goods Act is responsible for evaluating the provided information regarding the good including the essential, but not restricted to scientific data. This is conducted before the start of the clinical trial. The HREC takes into consideration scientific and ethical issues relating to the clinical trial protocol. It is the responsibility of the sponsor to notify the TGA of all the unapproved goods used in the clinical trial which have been approved in the CTA application.
Role of Trial Sponsors in the CTN and the CTA Schemes
Any clinical trial in Australiamust be sponsored by an Australian entity who is the trial sponsor. The sponsor can be an individual, company, organization, or institution. The trial sponsor is responsible for ensuring the goods to be used in the trial are approved. Generally, the sponsor takes full responsibility clinical trials conducted under the CTN and the CTA schemes.
Good Clinical Practice
Under the Therapeutic Goods Regulation of 1990, the usage of medicines and biologicals in a should be in agreement with the etsguidelines for good clinical practice. Before the start of any trial, both parties involved should be in consent and ensure that the rights, safety, and well-being of the trial participants are well upheld. On the onset of the trial, the sponsor is required to consult the HREC to determine whether exclusions under the CTN and the CTA schemes are required for the goods. In case exemptions are required, the sponsor takes responsibility to gain approval for the therapeutic goods to be used. The sponsor needs to consider whether the product is therapeutic, the type of the therapeutic product and whether the good is approved.
Generally, therapeutic goods for clinical trials are classified into four types; medicines, medical equipment, biological, and other therapeutic goods. Medicine is termed as goods acting as pharmacological, chemical, immunological, or metabolic means in or on the body. Medical devices are types of equipment intended to be used in medical procedures on human beings. Biological goods contain human cells or animal cells, tissues, or organs. Other therapeutic goods are neither classified as medical nor biological.
The clinical trial in Australia is comprised of the trial sponsors and the regulating authorities. The Human Research Ethics Committee specifically plays a unique role in the regulation of clinical trials. All clinical trials as mentioned earlier must be evaluated by the HREC. Under the CTN and the CTA schemes, the HREC is responsible for supervising the conduct of the clinical trials³. In case the HREC informs the principal investigator of deficiencies, the CTN and the CTA schemes require the ceasing of further use of the therapeutic goods. The HREC must additionally not provide advice to the sponsor that is inconsistent with the protocol of clinical trials.
Several circumstances may lead to the withdrawal of the therapeutic goods. Firstly, is the presence of evidence or recurrent deviation from the clinical protocol and which may lead to violation of the rights and welfare of the trial participants. Secondly, if it is evident that continuous partaking of the trial protocol caries unacceptable risk of death, serious injury, or illness to the trial participant.
3. “The Regulatory Environment,” Australian Clinical Trials, last modified October 11, 2020, https://www.australianclinicaltrials.gov.au/researchers/regulatory-environment.
The use of the goods may also be withdrawn if a comparative study shows that one treatment is risky, such that continuing with the trial may be a hindrance on one side of the participants. Lastly is if the trial is in breach of the state laws and regulations regarding clinical trials.
Role of Principal Investigators
The principal investigators should protect the rights and wellbeing of the participants under their care. They are responsible for supervising their entire research team. They must further ensure that the clinical trial is conducted within the clinical trial protocol. The prime investigator must further make certain that the medical cover is available and that all harmful effects of the trial are reported in accordance with the protocols. In case the principal investigator initiates the trial, they take they play the roleof the trial sponsor and are responsible for ensuring the GCP requirements are met.
Clinical Trials and Ethical Treatment of Subject
The clinical regulations in Australia are set about clearly to prevent any breach of contract. Regulated by the CTN and the CTA schemes, the therapeutic goods used in clinical trials involving human beings are sure to be safe⁴. The clinical guidelines contain provisions for the trial sponsors and the principal investigators to protect the rights and interests of the trial participant.
The sponsor is responsible for evaluating whether the goods to be used are therapeutic and check whether they are approved under the TGA. If the goods are not approved for supply in the trial, the sponsor should follow the process outlined to ensure the goods are approved by the relevant authorities. 4. “Clinical Research Regulation For Australia,” ClinRegs, accessed April 17, 2021, https://clinregs.niaid.nih.gov/country/australia#_top. The principal investigator on the other hand ensures the welfare and safety of the trial participant. Any deficiencies in the trial process must be reported to the Therapeutic Goods Act authority⁵. In the Australian clinical handbook, conditions for withdrawal of the therapeutic goods are set out clearly as explained earlier. This is especially if there is a possibility that the trial is likely to lead to death or endanger the health of the trial participant.
It is thus evident that the clinical regulations in Australia appreciate the ethical treatment of the trial subject. The safety of the trial subject is thus at the first interest of all the parties involved. The guidelines provided are keen to ensure the quality of the clinical trials is not compromised in any way. Clinical trial practice in Australia is therefore ethical.
5. “clinical research regulations for Australia”
“Clinical Research Regulation For Australia.” ClinRegs. Accessed April 17, 2021. https://clinregs.niaid.nih.gov/country/australia#_top.
Pinder, Tobey-Ann, and Dilip Ghosh. “Complementary medicine regulation in Australia.” Nutraceutical and Functional Food Regulations in the United States and around the World, 2019, 387-398. doi:10.1016/b978-0-12-816467-9.00025-3.
Potent, Keith. “The future of phage clinical trials in Australia.” Microbiology Australia 40, no. 1 (2019), 16. doi:10.1071/ma19004.
“The Regulatory Environment.” Australian Clinical Trials. Last modified October 11, 2020. https://www.australianclinicaltrials.gov.au/researchers/regulatory-environment.