US Federal Appeals Court Sides with FDA: Propagated Stem Cells Are a Drug

USA v Regenerative SciencesA long-standing debate in the commercial stem cell arena has focused on whether stem cells grown in a lab prior to clinical use as a transplantation product are biological drugs subject to full FDA vetting. The alternative view has been that such stem cell products are not drugs, but rather are simple human cellular and tissue products.

That debate, at least operatively, would seem to be over with a ruling today by the federal D.C. Court of Appeals supporting the FDA position that stem cells grown in a lab are in fact drugs. The decision came on an appeal of a lower district court ruling in USA v. Regenerative Sciences case, which had also supported the FDA position.

Judge Griffith, writing for the majority of the Appeals Court:

GRIFFITH, Circuit Judge: In this civil enforcement action, we must decide whether the appellants—three individuals and a related corporate entity—violated federal laws regulating the manufacture and labeling of drugs and biological products by producing, as part of their medical practice, a substance consisting of a mixture of a patient’s stem cells and the antibiotic doxycycline. Because we conclude that they did, we affirm the district court’s judgment and the permanent injunction it entered against appellants.

The Court also described the Regenerative Sciences procedure:

The Procedure begins with the extraction of a sample of a patient’s bone marrow or synovial fluid. From that sample, Regenerative Sciences isolates mesenchymal stem cells (MSCs), which are capable of differentiating into bone and cartilage cells. The MSCs are then placed in a solution to culture them—that is, to cause them to divide and proliferate.

Other substances are sometimes added to the solution that affect the MSCs’ differentiation. The culturing process determines the growth and biological characteristics of the resulting cell population. When the MSCs are sufficiently numerous for re-injection, they are combined with doxycycline, an antibiotic obtained in interstate commerce and used to prevent bacterial contamination of the MSCs. The resulting mixture (the Mixture) is injected into the patient from whom the stem cell sample was initially taken, at the site of the damaged tissue.

In its ruling the Court emphasized it was not simply deferring to the FDA opinion on the matter, but made the ruling based on evidence.

I asked Dr. Chris Centeno, the leader of Regenerative Sciences, a few questions about his reaction to today’s ruling.

What’s your take on the ruling? Centeno: The DC Circuit agreed with the FDA’s position. Not much more to it.

Was it just a “yes/no” kind of situation or are there subtleties to what the court said? Centeno: They basically said that a physician producing what the FDA considers a drug (in our case culturing autologous MSCs) is subject to FDA federal drug rules and isn’t practicing medicine.

What’s next for Regenerative Sciences? Appeal to Supreme Court? What would that entail? Centeno: We will abide by their ruling as we have done since August of 2010. At that time we got our first written indication of a formal FDA position and we complied by no longer culturing cells at our Colorado medical practice. We will make every effort to continue to comply and we will not pursue appeal to the Supreme Court.

The ruling along with Dr. Centeno’s indication of there most likely being no further appeal would seem to cement as the law of the land that propagated stem cells, even when used in an autologous context, are drugs, particularly when mixed with other substances or in other ways more than minimally manipulated. This development confirms my #8 prediction for the stem cell field for 2014 and I support this ruling.

USA v Regenerative Sciences Word Clouds are Illuminating

By Paul Knoepfler and Lakshmi Bharadwaj

What can clouds tell us about stem cell legal court case strategy?

It turns out, quite a lot.

In about a week a Federal Appeals Court Case will begin to review the ruling in the USA v Regenerative Sciences that favored the FDA.

This is arguably one of the most important stem cell-related court cases in years and could have as far reaching implications as the Sherley v Sebelius Case, but of course in a different way.

Regen Sciences Case Cloud

The USA v Regenerative Sciences case has many components, but is focused primarily on one key question:

are stem cell-amplified stem cell products intended for autologous use a biological drug? 

The latest ruling in the case went in favor of USA and the FDA, essentially answering that question “yes”.

Will that decision be upheld on appeal or overturned?

The stakes are huge for the field.

The Appellant in this case, Regenerative Sciences, has a cultured stem cell product called Regenexx that the FDA has defined as a biological drug.

A number of filings have been made related to this case including an Appelle’s Brief (USA stating its case) and an Appellant’s Brief (Regenerative Sciences stating its case).

In its court filing, Regenerative Sciences asks:

Is the Cultured Regenexx Procedure the manufacturing of a drug as defined by Federal law or the practice of medicine as defined by State law?

At the top of this post is a word cloud of the Appellant’s Brief. Below is a word cloud of the Appellee’s Brief.

They are very different and in fascinating and telling ways.

FDA Word Cloud

To me, the Regenerative Sciences Cloud suggests their areas of focus in the case (with major cloud words in bold here): the FDA, State level regulation of stem cells, and the practice of medicine rather than a biological drug. The words District Court are also very prominent. This is the court whose ruling went against them so it is not surprising they would be heavily mentioned.

The USA/FDA Cloud is quite different, more narrowly focused far more prominently on fewer main words: drug product and defendant. Some smaller, but still major words here include U.S.C., USCA, FDCA, Culture, Manufacture and Manipulate. Other smaller but still prominent words include cell and regulateIt seems the USA is emphasizing their assertion that this is a manufactured, manipulated cellular drug product because it spends time in culture, and asserting that their authority to regulate stem cells arises from specific Act’s and such.

These word clouds are not who is right or wrong in the case or who will win or lose, but rather to me they simply and elegantly tell us some things about respective strategies in the case.

What I found missing (or only present as very tiny) in both clouds that was particularly notable was safety and I would have liked to have seen the word patient be larger in both.

Paul wrote this piece and Lakshmi did the word cloud text mining analysis.