Abstract
Cell and tissue-based products, such as autologous adult stem cells, are being prescribed by physicians across the world for diseases and illnesses that they have neither been approved for or been demonstrated as safe and effective in formal clinical trials. These doctors often form part of informal transnational networks that exploit differences and similarities in the regulatory systems across geographical contexts. In this paper, we examine the regulatory infrastructure of five geographically diverse but socio-economically comparable countries with the aim of identifying similarities and differences in how these products are regulated and governed within clinical contexts. We find that while there are many subtle technical differences in how these regulations are implemented, they are sufficiently similar that it is difficult to explain why these practices appear more prevalent in some countries and not in others. We conclude with suggestions for how international governance frameworks might be improved to discourage the exploitation of vulnerable patient populations while enabling innovation in the clinical application of cellular therapies.
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Notes
Includes the separation of tissue, mincing of tissue, separation of cells, isolation of specified cells, treatment by antibiotics, rinsing, sterilization by gamma-rays etc., freezing, and thawing. See Guidelines on Ensuring Quality and Safety of Products Derived from Processed Cell/Tissue (PFSB/MHLW) Notifications, 2008.
Part 3-2A of the Therapeutic Goods Act 1989 defines biologics as “a thing made from, or that contains, human cells or human tissues and that is used to treat or prevent disease, ailment, defect or injury; diagnose a condition of a person; alter the physiological processes of a person; test the susceptibility of a person to disease; or replace or modify a person’s body parts” (Therapeutic Goods Act 1989: No 20, 1990, p169-170).
Medical devices are defined in the Schedule as “any instrument, apparatus, implement, machine, appliance, implant, in vitro reagent or calibrator, software, material or other similar or related article” and cosmetic products are “any substance or preparation that is intended by its manufacturer to be placed in contact with the various external parts of the human body or with the teeth or the mucous membranes of the oral cavity.” Thus, while a point-of-care cell processing device may fall within the scope of the Act, the cells processed using this technology would not (Health Products Act [2007] Part 1 Section 4[1]).
In 2007, Drs Georgia Lee and Low Chai Ling were censured for offering aesthetic treatments with stem cell “extracts” without evidence of efficacy (High Court of Singapore 2012); Dr Martin Huang Hsiang Shui in 2009, for offering therapies involving the injection of xenogenic (animal) foetal cells into patients for anti-ageing and rejuvenation purposes (Singapore Medical Council 2009); and Dr Wong Yoke Meng in 2010, for offering stem cell-based “anti-aging” products and therapies that were not medically proven (Singapore Medical Council 2010).
Non-substantial manipulation includes cutting, grinding, shaping, centrifugation, soaking in antibiotic or antimicrobial solutions, sterilization, irradiation, cell separation, concentration or purification, filtering, lyophilization, freezing, cryopreservation, and vitrification (EC Regulation No 1394/2007 Annex I).
See the Expanded Access Program in the US at http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/AccesstoInvestigationalDrugs/ucm176098.htm; the Named Patients Access programme in Japan; the Special Access Scheme in Australia at http://www.tga.gov.au/hp/access-sas.htm; the U.K. Specials Scheme at http://www.mhra.gov.uk/Howweregulate/Medicines/Doesmyproductneedalicence/Medicinesthatdonotneedalicence/index.htm, and the Hospital Exemption Scheme at http://www.mhra.gov.uk/home/groups/es-policy/documents/publication/con065623.pdf. Singapore does not have a formal programme, but the regulator has the discretion to apply similar arrangements; see http://www.hsa.gov.sg/publish/hsaportal/en/health_products_regulation/safety_information/product_safety_alerts/2008/update_on_aprotinin.html.
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Lysaght, T., Kerridge, I.H., Sipp, D. et al. Ethical and Regulatory Challenges with Autologous Adult Stem Cells: A Comparative Review of International Regulations. Bioethical Inquiry 14, 261–273 (2017). https://doi.org/10.1007/s11673-017-9776-y
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DOI: https://doi.org/10.1007/s11673-017-9776-y