DC Court Says that Stem Cells are Drugs


On the 23rd of July, 2012, the US District Court in Washington DC acknowledged the right of the Food and Drug Administration (FDA) to regulate clinical therapies that are made from the patient’s own processed stem cells. This case answered the question, “Does the court agree with the FDA that stem cells are drugs?”

According to the judge, the FDA is right and stem cells cultured outside the body are drugs. This ruling upholds the injunction brought by the FDA against Regenerative Sciences, the Broomfield, Colorado-based clinic that offers the Regenexx stem cell treatment procedure.

The Regenexx procedure uses mesenchymal stem cells that are isolated from patients’ bone marrow. These stem cells are then processed and injected back into the patients to treat joint pain. The FDA has labeled this procedure the “manufacturing, holding for sale, and distribution of an unapproved biological drug product.” In August 2010, the FDA ordered Regenerative Sciences to stop offering the treatment, since they were offering a drug without FDA approval

According Nature magazine science reporter, David Cyanoski, investigations by the FDA that led to the injunction showed that there were flaws in the cell processing protocol that violated the FDA’s regulations that refer to “adulteration.” These regulations are meant to ensure the safety of patients who receive the therapy.

Not surprisingly, academics are praising the decision and a shot across the bow of any enterprising physician who wants to offer stem cell treatments. For example, Jeanne Loring, a regenerative-medicine scientist at the Scripps Research Institute in La Jolla, California, has said that this court decision will send a warning to others who want to offer unapproved stem-cell treatments. In her words: “So many people want to start these companies. They say, ‘FDA? What FDA?’.”

Chris Centeno, the medical director of Regenerative Sciences and one of two majority shareholders, told Nature that he plans to appeal against the ruling. Centeno has replied to the ruling in an internet book entitled “The Stem Cells They Do Not Want You To Have.” Centeno’s main objection during the trial was that the ‘Regenexx’ procedure does not significantly modify the mesenchymal stem cells before they are reinjected into the patient. Therefore, the procedure should be considered a routine medical procedure. The company also argued that because all the processing work is done in Colorado, the procedure should be subject to state law, rather than to regulation by the FDA.

Unfortunately for Centeno, the Ninth Circuit court disagreed with both arguments. According to the court: “the biological characteristics of the cells change during the process.” This and other considerations mean that the cells are more than “minimally manipulated,” which makes them a drug a subject to regulation by the FDA. .

University of Minnesota bioethicist Leigh Turner, agrees with the court on this one. Turner noted: “It is much too simplistic to think that stem cells are removed from the body and then returned to the body without a ‘manufacturing process’ that includes risk of transmission of communicable diseases,” he says. “Maintaining the FDA’s role as watchdog and regulatory authority is imperative.”

The FDA injunction only applies to one of the Regenexx stem-cell products; the Regenexx-C procedure. In this procedure, the bone marrow mesenchymal stem cells are processed for 4–6 weeks. The Regenexx-C procedure will still be available, since after the 2010 injunction, the company moved its treatment location to an affiliated Cayman Island clinic.

Centeno plans to continue providing the other three procedures; Regenexx-SD, Regenexx-AD, and Regenexx-SCP, for joint pain, in the United States. In those treatments, the cells are reinjected within one-two days. Centeno claims that those cells are “minimally manipulated”, and that the FDA sees them as the “practice of medicine” and “has no issues” with them.

According the Nature’s David Cyanoski, until July 25th of this year, a graphic on the Regenerative Sciences website claimed that these three other procedures were “FDA approved.” However, the FDA has not approved these three procedures, and Centeno was not able to provide documentation to support his claims that the agency views the three treatments as outside its purview. This graphic was removed from the Regenexx website after Nature’s enquiries.

Stem-cell ethics and regulation expert, Doug Sipp, who is at the RIKEN Centre for Developmental Biology in Kobe, Japan, is concerned that this ruling will simply drive entrepreneurs to move their stem cell clinics outside the United States to avoid regulation. Indeed, Regenerative Sciences has done just that by setting up their Regenexx-C procedure in the Cayman Islands. According to Sipp, “Other US stem-cell outfits have close ties with partner clinics in Mexico and other neighboring countries, which are traditionally regulatory havens for other forms of fringe medicine as well. I suppose it will be business as usual in such places,”
We will have more to say about this in the days to come, but for now, this is it.

The FDA is Responsible for the Drug Shortages


The Food and Drug Administration (FDA) has implemented extremely restrictive drug policies that are generating drug shortages across the nation. According to the Regenexx blog, clinicians all over the United States have been feeling the effects of this pinch for some time.

Centeno gives the following example: “we were paying about $1 a bottle for local anesthetic, now when we can find it-that same bottle is often $4 a bottle.” As you might guess, this is having a significant effect on patient care, since surgery centers cannot get their hands on certain drugs. Cancer patients have been dramatically affected, since stocks of cheap, generic drugs are drying up.

On his blog, Centeno predicted that these shortages were due to “an ascendant hyper-regulatory FDA.” As it turns out, Centeno’s instincts were dead on. A Congressional hearing has confirmed that the FDA is responsible for the drug shortages. The “new FDA” focuses on reducing the so-called “type 1 regulatory” errors. Type 1 regulatory errors occur if a dangerous drug is allowed to go through market. It is certainly a proper function of the FDA to prevent type 1 regulatory errors. However, by overly focusing on type 1 regulatory errors, the agency is guilty of type 2 errors, in which good drugs are from the market.

The number of people harmed by type 2 errors is very large indeed. One estimate puts the number at 82,000 lives a year. Forbes Magazine documented the enormous rise in Warning Letters issued by the FDA. These Warning Letters have essentially shut down the production of generic drugs. These factories were shut down not because there was an actual problem, but because of theoretical risks due to current Good Manufacturing Practice violations.

The FDA employees that issued the letters did not take into account the consequences of their actions; namely that entire factories would have to shut down. A fair number of these manufacturers may or may not be able to reopen their production lines for these cheap medications because of the increased regulatory costs. Some of these companies may even have had to build new facilities. Many companies will simply drop the production line and this means less generic drugs. Also for many of these drugs, there are no brand name alternatives anymore, and the consequences of all this is that our hyper-regulatory FDA that has chosen to focus on reducing one type of regulatory error and by being only focused in one direction, they place the public’s health at risk.

What is the solution? We need a FDA that is as concerned with type 1 errors as they are with type 2 errors. This will balance these concerns so that the public is as protected from bad drugs as much as it’s protected from delays in promising therapies or shortages of generic drugs.