What Do I Need To Know About the Australian Regulatory Environment?
The TGA seeks to remain consistent with clinical trial guidelines introduced by the EMA, FDA, and ICH to enable streamlined approaches to clinical trial compliance. One important distinction is how the TGA navigates clinical trial approval. There are two distinct pathways available for trial applicants:
- Clinical Trials Notification (CTN): When following the CTN pathway, drug sponsors complete an online notification form and pay a fee prior to using their therapeutic in a clinical trial. An ethics board will review the proposed protocol and any supplemental data to make a risk/benefit assessment. Once approved by ethics, a notification is sent to the TGA. This is a rapid process that generally takes approximately 5 to 6 weeks from submission to approval.
- Clinical Trials Approval (CTA): The CTA pathway requires the paper submission of two forms with supporting preclinical or clinical data to seek approval from the TGA prior to beginning a clinical trial. This pathway is typically reserved for high-risk products and requires a 30- to 50-day review from the TGA, which more closely resembles an IND process than the CTN pathway.
In Australia, the TGA considers CGT products to be advanced therapies which includes:
- Gene therapies, in which the substance is used in or administered to humans to regulate, repair, replace, add, or delete a genetic sequence
- Gene therapies in which the substance is involved in the therapeutic, prophylactic, or diagnostic effect of the product
- Gene-modified cell therapies
- Any of the above in combination with a device
- Cell and tissue therapies that are Class 3 or 4 biologicals
Advanced therapies are then further regulated as either biologicals or prescription medicines. Gene therapies that involve ex-vivo manipulation of human cells (e.g. CAR-T cells) are regulated as biologicals. Other products regulated as biologicals include human cell and tissue-based therapeutic goods as well as live animal cells, tissues, and organs. On the other hand, therapies that involve in-vivo genetic manipulation of human cells are regulated as prescription medicines, including small silencing RNAs, CRISPR, and gene therapies administered by vectors. It should be noted that any biological or prescription medicine that involves a genetically modified organism (GMO) must also be approved by the Office of the Gene Technology Regulator (OGTR).
Biologicals are further categorized into 4 different classes based on intended use, level of manipulation and associated risk with Class 1 Biologicals being low risk and Class 4 Biologicals high risk.
So, with these classifications in mind, which of the aforementioned categories will need to undergo the longer CTA submission pathway? Largely, the CTA route is reserved for Class 4 biologicals due to their associated risk. According to TGA classification, Class 4 biologicals include:
- Biologicals that contain live animal cells, tissues, or organs
- Biologicals that comprise, contain, or are derived from human cells or tissues that have been modified to artificially introduce a function or functions of the tissues or cells in which the artificially introduced function or functions was not intrinsic to the cells or tissues collected from the donor
- Pluripotent stem cells
- Biologicals derived from pluripotent stem cells.
All biologicals that fit these criteria must receive clinical trial approval via the CTA scheme unless sponsors provide supporting evidence of the product safety from a previous clinical trial or evidence that approval has been granted to conduct clinical trials in an equivalent indication from a national regulatory body with comparable regulatory requirements, e.g., the FDA, EMA, PMDA. Although under these circumstances, approval via CTA pathway may not be mandated, ethics may still recommend it.
What Are The Benefits Of Conducting My Clinical Trial In Australia?
In addition to the streamlined regulatory framework, the following factors have also contributed to Australia’s emergence as a global hub within the APAC region for CGT clinical trials:
High-quality research and clinical trial Infrastructure
Australia boasts world-class research institutions and universities that are at the forefront of biomedical research. Institutions like the Garvan Institute and the Peter MacCallum Cancer Centre are leading in gene therapy and cellular research. Australia also has well-established clinical research facilities and hospitals equipped with the latest technology, which supports the rigorous demands of clinical trials. There are several existing clinical trial sites with previous experience conducting CAR-T, CRISPR, and viral vectored gene therapies. In addition, full service CRO’s like Avance clinical provide excellence in all aspects of CGT clinical trial support from preclinical consulting, assistance with regulatory submissions across the globe and trial management through all phases of development. Avance Clinical’s objective is to collaborate with sponsors at an early timepoint to ensure that their corporate goals are met in an efficient manner to maximize return on investment whilst prioritizing patient safety. Prior to starting a clinical trial, the Avance clinical scientific and regulatory services team assesses a sponsors nonclinical/clinical data package to determine if there are any perceived challenges to clinical trial approval. A challenge with CGT’s is that although Australia follows ICH, EMA and FDA guidelines, the CGT landscape is evolving at a rapid rate with many new therapies not being adequately described in regulatory guidelines and often have a relatively unknown risk profile. Through an understanding of the products mechanism of action and potential limitations of nonclinical assays, our team of experts work with sponsors to identify any potential safety concerns so that their impact can be mitigated through careful clinical study design and appropriate monitoring.
CGT manufacturing capabilities
Australia has a proud and long history of onshore cell and gene therapy capabilities with Cell Therapies Pty Ltd having over 20 years’ experience in GMP manufacturing of cell therapies for clinical trial and commercial supply. Australia is currently expanding its CGT manufacturing capabilities to establish Australia as a global hub for CGT clinical trials2-4. Some of the key attributes of the CGT manufacturing ecosystem in Australia include:
- Onshore manufacturing capability and capacity across cell and gene therapy manufacturing including TGA-licensed facilities (e.g. Cell Therapies Pty Ltd).
- For first in human (FIH) clinical studies in Australia, products do not need to be manufactured in GMP licensed facilities but must adhere to GMP principles to ensure safe products for patients. This helps to accelerate early clinical development of CGT as it acknowledges that sponsors are often still optimizing the manufacturing process for larger scale supply. This scheme supports a fast-to-fail approach, but developers must be mindful that progression to extended PhI trials or advancement to PhII trials will require a Technology Transfer to a licensed GMP manufacturer which is costly.
- TGA licensed GMP facilities for manufacture of critical CGT starting materials including plasmid DNA, viral vectors (onshore GMP capability in development such as the Viral Vector Manufacturing Facility (VVMF))) and mRNA (for in vivo and ex vivo gene therapies)
- Capabilities that support the whole product development pathway from FIH, early to Late phase clinical trials, through to commercial manufacturing capabilities, expertise, and experience that is hard to match anywhere else in the APAC region. This provides significant value-add to attract international investment to further grow onshore clinical trial activity.
- Close proximity to other CGT manufacturing sites in the APAC region (e.g. New Zealand).
Reputation for Quality
Australia’s commitment to high standards in healthcare and research adds credibility, making it an attractive location for international sponsors looking to conduct trials with clinical trial data from studies conducted in Australia being recognized by all major regulators across the globe.
Diverse patient population
Australia’s multicultural population allows for diverse recruitment opportunities, making it easier to study a wide range of conditions and responses to therapies. Australia also provides centralized access to clinical trial sites and patients in other nearby APAC countries.
Cost Savings
Another attractive advantage of conducting CGT trials in Australia is the R&D tax incentive, which if eligible, provides sponsors the potential of a 43 % rebate on clinical study costs. Avance Clinical can recommend local tax consultants who can advise clients on whether they are eligible for this benefit and how to make a claim to save costs.
What Considerations Are Important For The Broader APAC Region?
Australia is ideally positioned as a central location for access to patients and clinical trial sites in the broader APAC region. With CGT clinical trial experience and similar streamlined regulatory processes for innovative therapies, countries such as New Zealand, Japan, South Korea, Taiwan and Singapore further add to the potential patient pool and cultural diversity which is important for later phase studies. With clinical staff located in New Zealand, South Korea and Taiwan and a global regulatory team with experience in submissions to MEDSAFE, PMDA, MFDS, TFDA and HSA, clinical CRO’s like Avance clinical can facilitate submissions and manage the addition of clinical study sites within these countries. This capability is further bolstered by a partnership between Avance clinical and Cell therapies who can not only support domestic supply of CGT products but are approved for the commercial supply of regenerative medicines by Japan’s PMDA, and approved by Singapore’s HSAAS and audited by South Korea’s MFDS for commercial supply of T cell products.
What’s Next?
Though conducting a trial in the APAC region may initially seem like a challenge for emerging U.S. biotechs, the benefits are ample. In Australia, there are a wide range of clinical trial sites, experienced clinical researchers, manufacturing infrastructure, and qualified CRO and CDMO partners like Avance Clinical and Cell Ttherapies that will provide full support for conducting CGT clinical studies. Furthermore, conducting your clinical trial in Australia yields major cost savings. If your team is interested in hosting a clinical trial in Australia or the broader APAC region, opt to work with a CRO partner that will guide you through each phase of your trial and guarantee quality and regulatory compliance.
References
Market Research Future, https://www.marketresearchfuture.com/. (2024, September). Asia Pacific Cro Market Size, trends, growth, report 2032. Asia Pacific CRO Market Size, Trends, Growth, Report 2032. https://www.marketresearchfuture.com/reports/asia-pacific-cro-market-12642#:~:text=Pacific%20CRO%20Market%3F-,The%20Asia%20Pacific%20CRO%20Market%20size%20was%20valued%20at%20USD,forecast%20period%2C%202024%2D2032.
https://www.ausbiotech.org/documents/item/768
https://www.ausbiotech.org/documents/item/666
https://www.ausbiotech.org/documents/item/664
