Made by cells for cells - extracellular vesicles as next-generation mainstream medicines.

Current medicine has only taken us so far in reducing disease and tissue damage. Extracellular vesicles (EVs), which are membranous nanostructures produced naturally by cells, have been hailed as a next-generation medicine. EVs deliver various biomolecules, including proteins, lipids and nucleic acids, which can influence the behaviour of specific target cells. Since EVs not only mirror composition of their parent cells but also modify the recipient cells, they can be used in three key areas of medicine: regenerative medicine, disease detection and drug delivery. In this Review, we discuss the transformational and translational progress witnessed in EV-based medicine to date, focusing on two key elements: the mechanisms by which EVs aid tissue repair (for example, skin and bone tissue regeneration) and the potential of EVs to detect diseases at an early stage with high sensitivity and specificity (for example, detection of glioblastoma). Furthermore, we describe the progress and results of clinical trials of EVs and demonstrate the benefits of EVs when compared with traditional medicine, including cell therapy in regenerative medicine and solid biopsy in disease detection. Finally, we present the challenges, opportunities and regulatory framework confronting the clinical application of EV-based products.

Challenging Pandemic Law: From Vaccine Mandates to Judicial Review of Vaccine Approvals.

Over recent years, dozens of legal challenges have been instituted in response to government action during the COVID-19 pandemic. While public health orders have been challenged on several grounds, few cases have succeeded. Fewer cases still have called into question decisions made by the Therapeutic Goods Administration (TGA) to approve the COVID-19 vaccines. This section provides a brief update on one recent, partially successful COVID-19 health directions case before examining two applications in the Federal Court of Australia seeking judicial review of the TGA's approval of the COVID-19 vaccines. The section argues that, while both TGA applications were dismissed for lack of standing, they illustrate how and why third parties will ordinarily not be entitled to challenge administrative decisions about therapeutic goods.

Sexual Boundary Violations by Doctors - Context, Regulatory Consequences and Preventive Strategies.

While sexual boundary violations by doctors (SBVs) are viewed with utmost seriousness by disciplinary bodies and tribunals, complaints of SBVs in Australia continue to increase. In 2023, the Australian Health Practitioner Regulation Agency (Ahpra) outlined a "blueprint" to protect patients better from sexual misconduct in healthcare: reform being considered in 2024, by Australian health ministers. Few analyses or studies have offered an overview of the prevalence, effects, and causes of SBVs, nor the duties, liabilities, possible disciplinary action against, and potential treatment of, doctors who commit them. This column offers such an overview, and considers, additionally, whether doctors who may have psychiatric disorders associated with their boundary violations would be suitable candidates for treatment. Ultimately, we contend that a purely "responsive" approach is inadequate, and preventive measures such as screening and more effective education should be considered in medical schools as a way of reducing the incidence of SBVs.

Throwing a Cat among the Pridgeon(s): The New South Wales Court of Appeal and the Public Interest Test under the Health Practitioner Regulation National Law.

This section examines the 2022 decision of Pridgeon v Medical Council of New South Wales in the New South Wales Court of Appeal that has taken a fundamentally different view of the public interest test employed in immediate action hearings under the Health Practitioner Regulation National Law. The section starts by examining the case and then looks at the approach taken by subsequent decisions. It will argue that the decision is substantially at odds with earlier authorities from all around Australia and fails to understand properly the meaning and purpose of the test.

How Should We Regulate Heritable Human Genome Editing in Australia?

Heritable human genome editing is a form of modification of the human genome that will be inherited by progeny of the person whose DNA has been edited. Editing human genomes in ways that are heritable is currently prohibited in many countries throughout the world, including in Australia. This section starts with an examination of the historical backdrop to Australia's current laws relating to heritable human genome editing, with particular focus on how technological advances and community responses have shaped our legislative environment for innovative artificial reproductive technologies. The section then examines how community responses to current developments in heritable human genome editing might shape future law reform. The aim is to provide a foundation for examining how the future regulatory environment for heritable human genome editing in Australia might be shaped in ways that are responsive both to technological developments and to contemporary ethical norms and social values.

A New Priority Pathway for Biologicals in Australia: Contextualising and Evaluating the Proposed Reforms.

This section examines recent reforms to the regulatory framework for biologicals contained in the Therapeutic Goods Act 1989 (Cth) in the context of the "New Frontier" of reform envisioned in a report completed by the Commonwealth Government in 2021. It compares Australia's proposed reform of the approval processes for biologicals to similar reforms that have been made over the last three decades in the United States and the European Union. It places the Australian reforms in the context of the commercialisation of regenerative medicine and identifies several potential shortcomings of the proposed reforms and reports on the current lack of data on the processes of expedited approvals in Australia more generally.

The Public Interest Test in Immediate Action Hearings under the Health Practitioner Regulation National Law.

This paper examines the public interest test and how it is employed in immediate action hearings under the Health Practitioner Regulation National Law. It examines the history of the test in New South Wales and its eventual adoption by other States and Territories. The paper then examines recent cases from across Australia to highlight differences of approach in the formulation and application of public interest in immediate action hearings. The section concludes with some reflections on whether further reforms are needed to clarify and improve the application of the test.

Unconventional Practice, "Innovative" Interventions and the National Law.

This column explores a recent health profession disciplinary case which throws light on the problems of unconventional interventions by medical practitioners under the Health Practitioner Regulation National Law Act 2009 (Qld). The case involved "innovative" practices which were later found to have been scientifically unsupported, dangerous to patients and grounds for cancelling the health practitioner's registration. This column looks at common features of these kinds of cases in Australia and then examines recent attempts by the Medical Board of Australia to draft policy guidance around the use of unconventional practice in medicine. This column concludes with a number of changes to improve the effectiveness of the proposed policy.

Promoting the personal importation of therapeutic goods: recent legislative amendments to advertising regulations may impact consumer access and understanding.

Objective The personal importation scheme is a legislative mechanism that allows health consumers to import unapproved medicines under certain conditions. This article analyses the legal and policy basis for the scheme and considers how reforms to advertising laws for therapeutic goods may restrict communications about it. The article represents the first published analysis of the personal importation scheme's interaction with the communications of health professionals and buyer's clubs. It considers how these communications may be affected by legal amendments, particularly where unapproved medicines may be accessed through the scheme. Methods An examination of Australian therapeutic goods law concerning the personal importation scheme was conducted, including both the historical law and recent regulatory reforms. Illustrative tables were prepared to identify scheme-related advertising that may contravene therapeutic goods law. Risk estimates were allocated to several new legal rules to indicate whether health professionals or buyer's clubs would contravene these laws when promoting the scheme to health consumers for unapproved medicines. Results Representations made directly to the public by health practitioners or on buyer's clubs websites about accessing unapproved therapeutic goods through the personal importation scheme are likely to contravene one or more advertising laws. Conclusions The Therapeutic Goods Administration has very strong powers to initiate compliance or enforcement action for advertising breaches in Australia for many promotional practices. Arguably, in the age of the internet and in the context of emerging expensive medicines, these powers should not be used to restrict health practitioners or buyer's clubs from sharing information about the lawful personal importation scheme to health consumers in need. Nevertheless, the study finds that health practitioners who promote or refer to the availability of unapproved medicines through the personal importation scheme outside of a consultation are likely to contravene the law and may be subject to disciplinary or enforcement action.

Points to consider in the development of national human genome editing policy.

Clustered regularly interspaced short palindromic repeats and other genome editing technologies have the potential to transform the lives of people affected by genetic disorders for the better. However, it is widely recognised that they also raise large ethical and policy questions. The focus of this article is on how national genome editing policy might be developed in ways that give proper recognition to these big questions. The article first considers some of the regulatory challenges involved in dealing these big ethical and social questions, and also economic issues. It then reviews the outcomes of a series of major reports on genome editing from international expert bodies, with a particular focus on the work of the World Health Organization's expert committee on genome editing. The article then summarises five policy themes that have emerged from this review of the international reports together with a review of other literature, and the authors' engagement with members of the Australian public and with a wide range of experts across multiple disciplines. Each theme is accompanied by one to three pointers for policymakers to consider in developing genome editing policy.

Australian regulation of autologous human cell and tissue products: implications for commercial stem cell clinics.

In 2018, Australia's Therapeutic Goods Administration introduced regulatory reforms that set stricter criteria around the regulation of products derived from a patient's own cells and tissues, posing significant implications for clinics offering stem cell treatments. We review the regulatory framework and discuss its potential commercial implications, including the ambiguities that may arise from it in practice, as well as the likely impact it will have on product development and advertising practices in the future.

A novel scheme for graft allocation in non-heart beating donor renal transplantation.

Patients waiting more than 3 years for a renal transplant were ranked according to our novel Bristol and Region Allocation by Non-heart beating Donor Score (BRANDS). One kidney from 40 non-heart beating donors was allocated to the highest BRANDS long-waiter and the other kidney allocated according to the UK National Allocation Scheme (NAS). The scheme reduced the number of patients waiting more than 3 years by 20%. Despite longer dialysis time, greater sensitization and more human leukocyte antigen mismatches, BRANDS patients had equivalent 3-year graft survival (BRANDS 91%, NAS 97%, P=0.264) and patient survival (BRANDS 94%, NAS 92%, P=0.99). Results were similar to 242 synchronous recipients from heart-beating donors. Renal function was significantly lower in BRANDS recipients (40 vs. 62 mL/min/1.73 m2, P<0.0001). Transplanting long-waiting patients with kidneys from non-heart beating donors has reduced waiting times without compromising early outcomes. It is unclear if equivalent survival will be sustained in the long term.

Human leukocyte antigen and the allocation of kidneys from cadaver donors in the United Kingdom.

The national scheme currently used for the allocation of cadaver kidneys in the United Kingdom includes factors demonstrated to improve transplant outcome and promote equity in organ allocation. Introduced in 1998, the scheme is based on human leukocyte antigen matching, gives priority to children and highly sensitized patients, and incorporates features to assist transplantation in patients who are difficult to match. The scheme is open and transparent and subject to continuous audit and review to address any inequities in access to transplant that become apparent.

Factors affecting graft and patient survival after live donor kidney transplantation in the UK.

BACKGROUND: The outcome after living donor renal transplantation is superior to that for deceased donor transplantation, but the results are not uniformly successful. The factors responsible for the variable outcome after living donor transplantation have not been well defined. METHODS: UK Transplant Registry data were analyzed to determine the outcomes of 3142 first adult kidney transplants from living donors (71% genetically related and 29% unrelated) performed between 2000 and 2007 inclusive. Kaplan-Meier survival estimates were determined, and factors that might be associated with graft and patient survival were analyzed using Cox proportional hazards regression modeling. RESULTS: Patient survival at 5 years was better for recipients of grafts from related than unrelated donors (97% vs. 93%, P=0.0002), but conversely graft survival was better in recipients of genetically unrelated grafts (93% vs. 89%, P=0.06). After adjustment for the factors found to influence graft and patient survival, these differences were no longer apparent. In contrast to the expectations, the degree of human leukocyte antigen-A, -B, and -DR mismatch did not influence graft survival. Increasing donor age (but not recipient age), recipient diabetes, and grafts from adult offspring were independently associated with poorer patient survival in the first 3 years after transplantation. Poorer graft survival was independently associated with donor age older than 59 years, and female recipients. CONCLUSIONS: Advanced donor age, but not human leukocyte antigen mismatch, is associated with poorer outcome after live donor kidney transplantation. However, the results of live donor transplantation remain superior to deceased donor kidney transplantation.