Back in January, the Therapeutic Goods Administration (TGA) announced a public consultation on the matter of the clinical use and regulation of autologous stem cell transplants. I did not submit a response, but I wish I had. Fortunately many people far smarter and informed than I, did, and I am very keen to see what the outcome will be.
In my view, this public consultation marks a critical turning point in the future of Australia’s regenerative medicine industry. Clinics offering stem cell therapies for a very wide range of conditions have sprung up all over Australia. They are, almost without exception, money-making quackery. But as a public we don’t really seem to care – we love our stem cells almost as much as the sporting heroes that have received them. In truth, there is scant robust evidence of clinical efficacy, even Regeneus (whom I have written about previously) disclosed in its public offering document that its orthopedic stem cell therapy was no better than a placebo for pain scores (IPO prospectus, page 25), even if it was found to be safe (ignoring any initial administration issues).
That’s a hell of an expensive placebo.
To be clear, haematopoietic stem cell treatments from cord blood have been used for a couple of decades to treat certain comparatively rare diseases like childhood cancers and thalassemia. This is good medicine and is well-validated clinical science, and this is not what I am talking about when it comes to stem cell snake oil. Most of the rubbish clinical offerings involve cell therapies derived from stromal vascular fractions containing mesenchymal stem cells (MSCs) that are obtained during liposuction or platelets derived from peripheral blood. MSCs are potentially useful because they tend to differentiate into structural materials like bone, cartilage and blood vessels, a capability that can, at least in theory, be used to repair tissue damage. However, owing to the general lack of robust clinical trials – despite 1,000ds of treated patients – this has yet to be really proven.
At $10,000 or more a pop there is apparently just too much money in it to consider the patient foremost. Indeed to the general public it probably seems strange, even a bit arrogant, that a private clinic can offer such a sophisticated and complex therapy without any of the sort of clinical development burden or regulatory oversight, typical of drug development.
In my opinion, you would be right. This arrogance extends to physicians that seem to be very comfortable practicing completely out of their area of expertise.
Clinics get away with this because the TGA allows certain regulatory exemptions that were originally intended to eliminate the possibility that the regulation of biologics would interfere with established and proven medical procedures, such as a bone marrow transplant or blood platelet transfusion. In these instances, a medical procedure – supervised by a physician for an individual patient – is not subject to the oversight of the TGA because it is considered to be “practice of medicine”, and not a manufacturing activity. Such procedures also have a much lower risk profile, particularly the case for therapeutic applications that are considered to be a Class 2 ‘minimally manipulated’ procedure (such as a bone marrow transplant).
This exception framework, at its most fundamental level in the letter and spirit of the TGA, should not apply to corporate entities offering healthcare service provision to the general public – it is a physician and not a commercial exception. This is because in order for the exemption to apply, the entirety of the process has to be under physician supervision and this is simply not how companies work in terms of decision-making, chain of process ownership, use of 3rd party laboratory testing and patient risk management. The TGA exemptions are about critical care for a seriously sick patient, not spruiking an elective consumer product.
But the more fundamental question, particularly in the case of autologous MSC stem cell treatments – that is where the patient is injected with their own cells – is whether this new mode of medicine is safe, effective and within the scope of “minimally manipulated”. You don’t have to know much about the science of stem cells to imagine that extracting and expanding cells derived from your fat tissue and converting them into bone or cartilage is a fairly major transformation of a cell. Indeed a cell that becomes a new piece of bone or cartilage is totally manipulated, as it is no longer even a stem cell! This is, of course, what stem cells are supposed to do – they are “pluripotent” and are able to be transformed into a very wide variety of tissue types. But in order to extract, expand and ultimately deliver an MSC therapy, the functional nature of those cells (the internal cellular mechanisms, gene activation, etc.) must necessarily be fundamentally altered. Additionally, MSC therapies are often administered alongside certain growth factors that can have an enormous impact on the biological function of those administered cells.
In a recent(ish) case, the so-called “Centeno” case, the FDA asserted that an autologous MSC treatment offered in the United States exceeded the threshold of ‘minimally manipulated’ exemption under the Public Health Service Act (PHSA § 361), and the courts agreed, including on appeal. The FDA’s ‘minimally manipulated’ definition is virtually equivalent to the TGA’s Class 2 definition. The FDA’s characterisation of the manufacturing process used in a fairly “conventional” (by Australian standards) autologous stem cell therapy makes it defensibly clear that there are valid scientific concerns that the use of stem cells in a variety of commonly touted settings are far from the notionally safe definition of ‘minimally manipulated.’
The TGA has clearly taken notice, and rightly so.
For anyone interested, I have written a short white-paper on why I think the TGA needs to pay attention greater attention to stem cell therapies and why US FDA action warrants careful consideration here in Australia (comments, criticisms and corrections welcome). The TGA’s goal should not be to stifle innovation or deny patients innovative new treatments, and the TGA has shown reasonable sensitivity to these issues in the past. The objective should be to have an industry that is appropriately regulated (self-regulation has seemingly not yet worked), offers proven patient outcomes and is safe – or at least has a safety profile that is justifiable relative to the seriousness of a medical condition. Clearly an orthopedic cartilage repair job has a different set of patient implications to, say, Huntington’s or Parkinson’s disease, and this risk-benefit equation needs to be cautiously assessed.
As and aside note, it would appear that the Regenexx procedure that was banned by the US FDA, or at least a variant thereof, is on offer in Australia.
Might be a good place for the TGA to start…