A novel immunotherapy is garnering much excitement for its ability to treat cancers. Called Chimeric Antigen Receptor T-cell therapy, known as CAR-T, involves using a patient’s own (autologous), or another individual’s (allogenic) human cells to treat cancer. The process involves obtaining a patient’s blood, isolating the white blood cells, engineering cancer fighting cells into those cells, then returning the cells to the patient’s body. The cells that are returned to a patient include the T-cells (original white blood cells) and a CAR. The CAR-T cells will then attack the cancerous cells.
This article discusses the regulation of CAR-T therapy in Australia, including considerations for commercialising the product across the Australian states and territories in light of existing state-based human tissue regulation, and future liability risks.
Key takeaways for manufacturers and suppliers:
- Adequate protocols for the management of treatment must be put in place to ensure informed consent is obtained at the initial stage of collecting the patient’s blood cells, and each stage following.
- Manufacturers and suppliers should consider the concept of ownership in the cells at each stage of the process and cover any such transfer of ownership within patient authorities and/or consents.
- Due to the complicated process of extraction and manufacture, the classification of the tissue at each stage needs to be carefully considered within the confines of each of the state human tissue legislation.
- Advertising rules in respect of CAR-T may differ from state to state due to state-based legislation on human tissue.
- Similar to considerations for other products on the ARTG, manufacturers should ensure they provide adequate warnings at each stage of the treatment in respect of the risks of the therapy.
CAR-T therapy in Australia
In Australia, there are currently 3 CAR-T cell therapies approved for use by the Therapeutic Goods Administration (TGA): Kymriah® sponsored by Novartis, and Yescarta® and Tecartus® both sponsored by Gilead. These approved treatments are regulated as biologicals used for autologous treatment.
Regulation under the Therapeutic Goods Act as biologicals
The Therapeutic Goods Act 1989 (Cth) (TG Act) defines biologicals as a thing that either comprises, contains or is derived from human cells or human tissues, and is represented in any way to be, or is, for use in the treatment or prevention of a disease, making a medical diagnosis, modifying a physiological process in a person, testing the susceptibility of persons to a disease or ailment or in the replacement or modification of parts of the anatomy in persons (s 32A).
Following the extraction of the blood cells, the cells are frozen and taken to the facility at which they will become CAR-T cells. At this point under the Therapeutic Goods Regulations 1990 (Cth) (TG Regulations), they are deemed 'blood components', and later at the transformation into CAR-T cells, they are deemed biologicals and regulated under the TG Act accordingly.
Manufacturing requirements
The TGA has developed an Australian specific standard for the manufacture of biologicals, human blood and blood components and haematopoietic progenitor cells. The Standard sets out the general manufacturing and quality requirements for therapeutic goods comprising, derived from or containing human cells or tissues, and determine the consistency of product quality, including labelling quality.
As part of the registration evaluation process under the ARTG, the TGA must evaluate whether the manufacturing and quality control procedures used to manufacture the biological are acceptable (s 32DE(1)(e)). Once registered, the TGA must certify that manufacturing steps taken outside of Australia are acceptable (s 32EA and s 32EB).
State-based human tissue legislation
CAR-T is the result of human tissue and is therefore arguably covered by the prohibition on the trade of human tissue products. The acts broadly define 'Tissue' as including organs, parts of the human body and substances extracted from the human body.1 However, each state act has exceptions to this prohibition.
- New South Wales, Queensland, South Australia and Tasmania – there is an express exemption where the tissue has been subjected to processing or treatment and is supplied for use in accordance with the directions of a medical practitioner for therapeutic, medical or scientific purposes.2
- Australian Capital Territory – an exemption to the supply of tissue for consideration applies to tissue which has been processed or treated for therapeutic or scientific purposes, but this exception does not apply to blood or any of its constituents.3 It is possible for Ministerial approval to override this specific prohibition.4
- Northern Territory – supply of tissue for valuable consideration is prohibited, however similarly to the Australian Capital Territory, the Minister can authorise a person to enter a contract if satisfied that there are special considerations to do so.5
- Victoria – the selling and buying of tissue is prohibited unless the sale is to a person holding a permit to buy the tissue.6 It is unclear whether CAR-T once manufactured would constitute a tissue, noting it is not a substance “extracted” from the human body, owing to having been modified since its extraction.
- Western Australia – the supply of tissue for valuable consideration is prohibited, however the Governor may make an Order exempting products derived from tissue that has been subject to processing or treatment. Similarly to Victoria, it is unclear whether CAR-T would properly be considered a tissue given at its manufacturing completion, it is arguably substance extracted from the human body.
Advertising
Generally, biologicals cannot be advertised to the public,7 however can be advertised exclusively to health care professionals. Under the Queensland, Western Australian and Victorian tissue acts, advertisements relating to buying of tissue are prohibited, unless that proposed advertisement has been approved by the Minister and contains a statement to that effect.8 Arguably, in these states CAR-T therapy would not be able to be advertised to healthcare professionals due to the comprehensive ban in their relevant human tissue act.
Common law considerations
Under the common law, there are additional considerations that apply. Property rights to human tissue has previously been considered by the Australian courts. The earliest cases in this area concern who owns the human body after death. In Australia, the case of Re Cresswell [2019] 1 Qd R 403, Brown J determined that there were property rights in the samples of sperm that had been released from a deceased man. Her Honour found that despite the application of work or skill, property rights could still be found.
It is difficult to determine whether the same considerations in Re Cresswell would apply in circumstances where the tissue was taken from a live patient for medical purposes prior to being manufactured into therapy. However, noting the uncertainty, manufacturers should consider the concept of ownership in the cells at each stage of the process, and cover any such transfer of ownership within patient authorities and/or consents. This is likely to be a more significant issue in the case of allogenic as opposed to autologous CAR-T cells.
Liability risks
As a product on the ARTG (despite it potentially being the patient’s own tissue) appropriate warnings must be given by both clinicians involved and manufacturers. Adequate warnings as relevant to each patient should be provided at each stage of the process in compliance with the requirements of the Australian Consumer Law. Failing to do so could result in an action against the manufacturer or sponsor for a breach of the consumer guarantees or misleading and deceptive conduct claim under the ACL.
In addition to product liability risks, the treatment gives rise to medical liability issues. In particular, it is critical that informed consent be obtained by the administering practitioners at each stage of the process in order to legally and ethically remove the blood from a patient’s body prior to manipulation. The removal of blood cells without a patient’s consent gives rise to an action in battery under the common law and the failure of a doctor to disclose information regarding side effects and risks can give rise to an action in negligence.9
1 Transplantation and Anatomy Act 1979 (Qld), s 4; Human Tissue Act 1983 (NSW), s 4; Human Tissue Act 1982 (Vic), s 3; Transplantation and Anatomy Act 1983 (SA), s 5; Human Tissue Act 1985 (Tas), s 3; Human Tissue and Transplant Act 1982 (WA), s 3; Transplantation and Anatomy Act 1978 (ACT), s 4; Human Tissue Transplant Act 1979 (NT), s 4.
2 Transplantation and Anatomy Act 1979 (Qld), s 42AA(1); Human Tissue Act 1983 (NSW), s 32(2); Transplantation and Anatomy Act 1983 (SA), s 35(3); Human Tissue Act 1985 (Tas), s 27(2).
3 Transplantation and Anatomy Act 1978 (ACT), s 44(1), (2).
4 Transplantation and Anatomy Act 1978 (ACT), s 44(4).
5 Transplantation and Anatomy Act 1979 (NT), s 22E
6 Human Tissue Act 1982 (Vic), s38 and s39.
7 Therapeutic Goods Act 1989 (Cth), s 42DL(11).
8 Transplantation and Anatomy Act 1979 (Qld) s 41; Human Tissue Act 1982 (Vic), s40; Human Tissue and Transplant Act 1982 (WA), s 3-/
9 Rogers v Whitaker (1992) 175 CLR 479.
