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.

14 thoughts on “USA v Regenerative Sciences Word Clouds are Illuminating


  1. Will be interesting to see how this appeal goes – Hopefully Regenerative Sciences has the financial guns to keep this battle going – it’s tough to go up against a group with technically unlimited $$


  2. I agree, “safety” and “patient” are fine words. I also like words like “choice” and “freedom”. But such fine words are not relevant to the law in question.

    As a “patient” I like “practice of medicine” but I’m offended that my own cells have been called a “manufactured” “drug”. I’ll have you know that my cells are evolved and the FDA didn’t have anything at all to do with that… (If they did, I’d sue them!)


  3. Brian – My sentiments exactly. Thank you for putting it into words and posting it. I believe you speak for millions of those of us who are ill.


  4. Paul, this case is about whether the FDA can pretend that a physician using autologous cells in his or her own patients can be regulated like a big pharma company, despite a century of legislation and case law that prohibits FDA from having any control over what a doctor does or how he or she does it. It is in particular it is not about the definition of “more than” minimally manipulated nor how that is applied to anything. In effect, since physicians are already quadruple regulated (medical boards, public health depts, hospital privileges, tort system), can FDA quintuple regulate them when they use stem cells?

    On the safety side, you may have missed a few papers. Right now, we have published more safety data on the use of MSCs in arthritis (this medical procedure) than any other entity (worldwide), see http://www.ncbi.nlm.nih.gov/pubmed/19951252 and http://www.ncbi.nlm.nih.gov/pubmed/22023622. In fact, we voluntarily gave our primary source data for the n=339 safety study to a group of European researchers we didn’t know. They concluded that our safety data was the highest quality of any published and that the procedure was safer than FDA approved hyaluronic acid shots, see http://www.regenexx.com/2013/07/new-study-regenexx-c-safety-paper-is-the-best-of-the-best-in-published-stem-cell-papers-for-arthritis/ . So all of this has never been about patient safety.

    I can’t predict how the DC Circuit will rule. I can say that there are many patients (one above) who are watching this case. They don’t want a paternalistic FDA telling them what risks they can or can’t take with their own bodies, they want to be able to have free and unfettered access to their own cells. In fact, these same patients tried to recently send a message through the Stem Cell Person of the Year voting that they are tired (and sick) of having industry surrogates use them as poster children to protect commercial and private/public research grant interests.


  5. I can see where both sides are coming from… Practice of Medicine vs Regulations as defined by the relevant sections in 21 CFR.

    From a regulatory perspective, I see this case ending in two scenarios:
    1. Fits under the definition of “Practice of Medicine” – in which case, the FDA may or may enforce the medical device regulation for all products used to prep the cells for the treatment – I would imagine that not all of what Regenerative Sciences used were approved medical devices and would need to respond to a new set of warning letter items for using adulterated devices.
    2. Follows definitions discussed in the original case – in which case, more-than minimally manipulated HCT/Ps are, in fact, biologics, and require approval through BLA prior to use.

    Either way, the delivery of medicine is covered by some form of regulation by the FDA. The ruling would just shift the focus on WHO would be most impacted from existing regulations.


    • Soo,

      The FDA has been prohibited from having any say in what a doctor does or how he or she does it. So while the FDA can go after a manufacturer for promoting a device or drug off-label (except in NY where the FDA lost that case in the 2nd circuit), a doctor gets to use it as he or she sees fit. In addition everything we would use/ have used had FDA approval for human use (usually a 510K).


  6. I agree that allogeneic expanded cell products or mass produced expanded cell products (e.g., Mesoblast) should be regulated similarly to drugs, with notable differences. The problem is where to draw the line when patient’s own (autologous) cells are expanded. It probably should depend on the level of expansion and or differentiation/epigenetic conversion. Patient’s safty must remain central but I do not believe should necessarily require a level of regulation such as that the overall cost of production will make it unaffordable or significantly increase the cost of cell products and cell therapies also for relatively simple applications (i.e., orthopedic) such as those that Chris Centeno was performing. I believe the same safety results could be obtained with simple product release testing but without adding levels of complexity and costs that would further contribute to make our healthcare unsustainable. We are already over 2.5 trillion/year in the US, or 18% of the GTP, projected to become 4.4. trillion in the next 2 decades. I would hope that for minimally manipulated and expanded autologous cell products we could find a middle ground where patient’s safety remains central through appropriate product release criteria but where also we keep such therapies cost effective. It is likely that large commercial interests will push for raising the bar, but office based and hospital based practices should be allowed to operate helping one patient at the time and providing a safe, but accessible healthcare where appropriate.


    • Dear Camillo,
      You raise an interesting point about allogeniec treatments. Intuitively, it seems that allogeniec treatments might be subject to more “heavy handed” regulation than autologous treatments. But I don’t like the idea that allogeniec cell therapies should automatically be regarded as drug treatments. Is it conceivable that some allogeniec treatments might be characterized more like a blood transfusion in which case they should not be considered as a drug treatment? My preference would be for things to be regulated according to their actual physical/chemical, biological nature. Perhaps this is too subtle a thing to do?

      One thing that is important is that all the research that leads to a treatment (drug or otherwise) should be available to the public who are being treated. Patients should be a significant part of the process — valued for their intellectual input, not just as passive consumers/subjects.


      • fully agree … I was referring more to allogeneic cells that are large-scale produced after massive expansion protocols, cryopreserved and distributed for treatment at rempte sites, or epigenetically converted cells

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  8. Agree Camillo. We are rapidly heading toward a world of unsustainable hyper-regulation in medicine that will severely hamper innovation and eventually bankrupt the system. At the end of the day, it all comes down to this: “A loved one lies in the intensive care unit, dying of a heart condition. There is little hope for recovery and the family surrounds the patient, waiting for the inevitable. The doctor breaks the silence with new information. A study just published shows that stem cells in the patient’s own body might be used to offer a chance of hope, increasing the odds of walking out of the hospital to as high as 50/50. However, the doctor is unable to help, as federal regulations have tied his hands, making the patient’s own cells prescription drugs for which there is no FDA approval.”

    This is not the type of world I want, but this is the type of world the cell therapy industry and FDA are currently creating.


    • Agree Chris, next week is an important one for the future of regenerative medicine…. All the best and may reason prevail

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