ReportA roundtable on responsible innovation with autologous stem cells in Australia, Japan and Singapore
Introduction
Regulators internationally are facing challenges in providing timely access to innovative therapies with autologous cells, including stem cells, while delivering novel products that are demonstrably safe and effective. Limited types of stem cells are currently accepted as the standard of care in clinical practice (e.g., hematopoietic stem cell transplantation for leukemia). Although many novel cell-based interventions are being investigated in early clinical trials for a variety of human diseases and conditions (1), very few products have been approved for marketing or accepted as standard clinical care in major healthcare markets. Allogeneic and autologous mesenchymal stromal cells (MSCs) derived either from bone marrow or adipose (fat) tissue, and also referred to as a type of stem cell, are one of the most prominent sources of cells being investigated (2).
One problem with current regulatory frameworks is the lack of alignment and coordination between regulators with authority over various domains of the research and clinical innovation trajectory (e.g., product marketing and manufacturing versus its use in clinical practice versus research). This problem is exacerbated when viewed across international jurisdictions where national economic and geopolitical imperatives have prompted some regulators to lower the barriers to market regenerative medicine products, and medical practices and specialist care with cellular therapies, including stem cells, may be accredited and governed differently (3). Cell therapies are regulated in major healthcare markets under complex frameworks that involve multiple agencies and institutional actors that may differ depending on whether the source of cells is allogenic or autologous.
Although many differences exist in the technical language and legal structures that regulate clinical research and practice, many countries have adopted a similar ‘risk-based approach’ to the regulation of cellular products (4). The risk-based approach generally sets out an evidence-based pathway for the manufacture and marketing of stem cells as medicinal products while allowing patients to access interventions with human cells in the context of clinical care, even though they may lack the evidence necessary for market licensure. These interventions do not fall under the jurisdiction of drug regulatory authorities, but are instead regulated under separate governance frameworks for clinical practice. This ‘siloing’ of regulatory powers and the discrepancy between evidentiary standards may not only be hampering, and perhaps even disincentivizing, the translation of products that are demonstrably safe and effective, it may have also enabled the growth of an industry marketing stem cells direct to the consumer (DTC) through the creation of loopholes and weak regulation.
The DTC marketing of stem cells is well documented ([5], [6], [7], [8], [9], [10], [11]). An international survey found the highest prevalence of clinics in the USA, followed by India, Mexico, China, Australia, the United Kingdom, Thailand, Malaysia, Germany and Indonesia (3). Recent research in the USA (12), Australia and Japan (13) found that the majority of these clinics are marketing autologous sources of adipose and bone marrow–derived stem cells, which we collectively refer to as autologous stem cell (ASCs). Of great concern are the marketing of expanded and non-expanded ASC products that have not been approved for the treatment of medical conditions in any country and how these cells are being administered through some form of injection, including intravenous and intrathecal modes. The safety profile and risks associated with these administration methods are highly uncertain (14).
These challenges were discussed at a roundtable event held in Singapore, November 2017, that brought together 35 scientists, clinicians, regulators, legal scholars and bioethicists from Australia, the European Union, Japan and Singapore. The aim of the roundtable was to share and exchange knowledge on the regulation of ASCs and discuss potential solutions within a co-operative regulatory model that draws on lessons learned from the translation of bone marrow and cord blood products. The event was held as part of the 2017 Annual Symposium of Stem Cell Society, Singapore, and although discussions were primarily concerned with the innovative use of ASCs in Australia, Japan and Singapore, consideration was also given to the global contexts in which the DTC industry has emerged and the implications for stem cell science and cell therapies more broadly. In this report, we will outline some of the challenges identified in the clinical translation of ASC science and then propose some of the solutions discussed at the roundtable.
Section snippets
Challenges in translating ASC science
Translating stem cell science into safe and effective products is a challenge for regulators everywhere, especially as health consumers and clinicians demand more timely access to innovative therapies with stem cells. In response to these challenges, some regulators have introduced programs aimed at accelerating the market approval process for stem cell–derived interventions and providing clinicians and patients with faster access to products that have demonstrated some benefit and safety in
Potential solutions
Potential solutions to these problems discussed at the roundtable are framed within a co-operative regulatory model. As illustrated in Figure 1, this model features three domains of regulation that must work together: the traditional laws that protect consumers and punitively sanction unacceptable practices (negative regulation); the statutory regulations that enable product development and commercialization (permissive regulation); and the codes, standards and guidelines that encourage ethical
Future outlook
Discussions at the roundtable identified challenges and proposed potential solutions that might help to reduce unethical marketing and unprofessional practices while encouraging responsible innovation with ASCs. The proposed co-operative model may provide a broad framework for identifying the relevant institutional actors and regulatory instruments needed at both national and international levels to establish, implement and enforce evidence-based standards for cell processing and manufacturing,
Acknowledgements
This roundtable was organised by the Centre for Biomedical Ethics at the National University of Singapore in collaboration with the Stem Cell Society, Singapore, the Sydney Law School and the Centre for Stem Cell Systems, University of Melbourne, with funding from the Humanities and Social Sciences Fund of the Office of Deputy President (Research and Technology), National University of Singapore (WBS: R-171-000-055-646) and an Australian Research Council Linkage Project Grant (LP150100739). We
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