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A United States court decision delivered on July 23, 2012 confirmed FDA's assertion that stem cells are drugs. If you've read my previous post on Prochymal, you may be wondering why this is news. Well, this decision marks the latest episode in the continuing courtroom drama that began in 2008 when the FDA sent a warning letter to Regenerative Sciences (now Regenexx) regarding its autologous stem cell procedures, which extracts mesenchymal stem cells (MSCs) from the patient's bone marrow, expands them in culture for many weeks, and then infuses them back into the patient's body to promote healing or reduce chronic pain*. Regenexx refused to comply with the agency's warning and argued its procedure did not fall under FDA jurisdiction. The agency responded by slapping the company with a federal injunction in 2010 to block the procedure's use in the US. The injunction didn't actually do much because the company simply moved the procedure to an off-shore clinic while expanding related services in the US.
This regulatory saga focuses on whether MSCs are a medical product, in which case the FDA has jurisdiction over the production process; or a necessary step in medical procedure, in which case they are exempt from FDA regulations. The distinction between product and procedure hinges on the definition of "minimal" processing. Prochymal fell under government jurisdiction because it is intended for multi-national distribution, and also because it is a mass-produced cellular product that requires months of culturing and sophisticated purification steps. On the other hand, procedures like platelet concentration from blood or surgical transplants are considered minimally processed because they are typically same-day procedures and the tissues involved do not change in a significant way. But for the Regenexx case, the FDA argued that the patient's cells are not minimally processed because they are grown in a lab for many weeks before infusion and the properties of those cells may have changed, and the court agreed. Regenexx has indicated it will appeal the court's decision, so we may expect more legal wrangling in the coming years.
So, how much harm can such a procedure potentially cause? Are the risks high enough to justify government regulations? Autologous infusion is unlikely to cause tumors if freshly extracted cells are used because they are more mature and lineage-restricted. However, fresh extractions are probably a mixed bag of cells that contain few MSCs, which limits efficacy. But if MSCs are cultured and enriched before infusion, they may undergo transformation in culture and become cancerous. Also, lab culturing itself is not without risks. The cells may be contaminated with microbes, or the cells may die during the freeze-thaw cycle that accompanies storage and administration. But if proper clinical procedures are developed and stringently applied, then these risk can be significantly reduced. The trick is finding a facility that follows stringent guidelines, and this is an area where regulations may be beneficial.
Unfortunately, questions regarding what happens after the infusion often devolve into a game of roulette and most questions are answered with "that depends". It's nearly impossible to get meaningful, large-scale clinical data for an individualized procedure like MSC infusion to determine overall safety and efficacy because each MSC preparation will be unique to each patient. There's also no predicting what MSCs (fresh or cultured) may become or what they may do inside a person because we don't know how to control or monitor the cells once they're inside. If all goes well, MSCs are indeed awesome. They may help heal persistent injuries like arthritis, and everything may work as advertised. But there are also some cons to consider: the infusion may cause an aberrant, but benign, tissue mass to form at the wrong place; the cells may just all die and do nothing; or they may secrete active biomolecules that does something (we don't know specifically what).
The unspoken question in this debate is whether the public can be trusted to make an informed decision regarding this procedure. The FDA obviously doesn't think so. Before anybody gets insulted and fired up about personal liberties, let's keep in mind that patients can benefit from some quality control before the cells go into their bodies. If patients decide to try this procedure, they will have to assume whatever risks that may occur after the infusion and be prepared to deal with the consequences. But I think even the most fervent early adopter would hesitate to be the guinea pig for fringe medical practices. I also can't imagine anyone turning to these options unless conventional medical practices have failed, or seem too extreme or terrifying (relatively speaking). Money is another limiting factor. Let's not forget that fringe medical procedures are not covered by most medical insurance in the US and the patients themselves must bear the costs. Do people reasonably assess personal risks and perform due diligence when their health and thousands of dollars are at stake? Hmm...that depends.
*Just to list some examples, former US presidential candidate Rick Perry and Yankees pitcher Bartolo Colon have both undergone such procedures to relieve chronic joint pain.
Photo credit: some rights reserved by Larry Myhre via Flickr (http://www.flickr.com/photos/larrymyhre/6145780836/)
