Today begins the Annual Interventional Orthopedics Conference in Colorado, and up on the docket is a regulatory discussion. They’ll have the attorney who litigated the Regenerative Sciences case speak because this litigator is one of the world’s experts on the US regulation of stem cells. To that end, I’d like to follow-up on a recent blog post where I exposed a US-based cell-therapy network (CSN) that was planning to deploy culture-expanded stem cells in the U.S. The physicians in charge of that operation were recently interviewed and did a very good job of muddying the waters around the regulation of cell drugs to make any reasonable person confused. In essence, their entire argument was circular (begin with a false conclusion and wiggle around until you end up back there), or, as our Latin colleagues would say, circulus in demonstrando.
US Cell-Drug Regulations
Ever since the Regenerative Sciences case, it has been crystal clear that the manufacture of autologous culture-expanded stem cells in the U.S. constitutes the manufacture of a prescription drug. That hasn’t stopped at least one group (and likely a second) from trying to position this, instead, as something else. I covered one group called CSN on this blog a few weeks ago.
Since that time, the CSN principles who are responsible for creating these cell drugs and claiming that they aren’t really drugs were interviewed by Paul Knoepfler. They admitted that they were culture expanding cell drugs without proper FDA approval (an IND or BLA), but they were able to throw out enough smoke and mirrors and regulatory terminology that even I had to do a double take on their reasoning for why what they were offering was legal.
Let’s Dissect Out the Regulatory Doublespeak
The Knoepfler interview revealed that the group culture expanding stem cells believes that they don’t require FDA approval in the form of an IND or BLA because they are performing “IRB approved” experiments on humans to gather data for an IDE. While I know enough not to be fooled by the alphabet soup of FDA terminology, the average patient or physician does not. Hence, let’s dissect what they said.
What is an IDE?
An IDE is an FDA approval to perform a study on a device that requires full FDA approval. Most devices are approved via another process called a 510K, which is a quick approval because there is a predicate device (one similar to the new one) that is already on the market. However, a new device that raises safety concerns requires a clinical trial and must go through the IDE process.
In cell-based medicine, an example of a where an IDE would be needed is for a new device to create a new product that doesn’t exist on the market. So if you have a new machine that isolates X compound from the soup of blood and that machine doesn’t yet exist, you would need an IDE.
There is one problem with IDEs on biologic devices. The part of the FDA that issues them is called CDRH (the device group within FDA). However, the biologics part of FDA is called CBER and it has first right of refusal over all biologics devices that come through CDRH. What this means is that if a device creates a new biologic product, then CBER can step in and demand that it also needs an IND and BLA (full FDA approval in multistep clinical trials for a biologic drug).
The IDE/IND Shuffle
The Knoepfler interview exposed some interesting things. Here is a copy/paste of some of the responses of the clinic chain culturing cells:
“We are simultaneously preparing an IDE application for the cryobank process but want to compile reasonable safety and outcomes data before filing. We also need to complete our “IDE for point of care” application as a prerequisite to that application. This is a fairly tedious process and we’ve been working with the FDA for the last year and a half and are nearly complete in our tasks to get approval.”
Not sure where to begin with this statement. An IDE is an approval to begin a clinical trial on a device that may pose safety issues. Here the device is apparently a point-of-care device. So the concept of collecting data before you submit an IDE is nonsensical. In addition, the topic being discussed is the need for an IND to produce a culture-expanded cell drug. Since an IDE has nothing to do with producing a cell drug or a clinical trial for the same, this is true circular doublespeak. As an example, this is like saying you need a building permit to build a house, but, instead, you have obtained a permit to sell hot dogs. In fact, you want to sell some hot dogs before you get the permit to see how it goes.
Is It Legal to Perform a Study Using a Culture-Expanded Cell Drug Without a Drug-Study Approval?
As discussed above, to even perform a study on culture-expanded stem cells in humans in the U.S., you need a cell-drug approval. This is called an IND, an Investigational New Drug Application. When asked by Dr. Knoepfler whether the group has an IND, this was the response:
PK: Do you or your other business partners have an IND? A BLA?
PK: If not, why not?
CSN: Once we determine safety and efficacy, and which claims we wish to pursue, then we will be able to work with regulators to find the best way to help patients obtain access to their own cells stored or expanded under sterile conditions.
So no IND. The CSN comment is fascinating. It seems to imply that these culture-expanded cells will not be used, but this directly contradicts the video presentation, which stated that once the forms were signed, the unapproved cell drugs could be used in patients. So is CSN backing off of treating patients? Is CSN still claiming that it’s not treating patients since this is part of a study? If the latter, as discussed, just to perform the study would require an IND.
The upshot? Yikes! You gotta love a good circular argument where you start with a conclusion by just asserting it and then try to backfill that with a regulatory alphabet soup that most physicians won’t understand. I suspect the recent interview will only dig the FDA hole deeper for CSN.