Camillo Ricordi, MD, FNAI, explains how the outdated FDA classification of islets as cellular transplants has hindered progress in this field for patients with type 1 diabetes.
Unfortunately, in the United States the field of islet transplantation is near extinction, said Camillo Ricordi, MD, FNAI, a professor and director of the Diabetes Research Institute and Cell Transplant Center at the University of Miami, Florida.
Apart from organ shortages and the potential risks, what other barriers inhibit uptake of islet transplantation?
Well right now in the United States, our major problem is that we have outdated FDA regulations that classify islets as cellular transplants, while in the rest of the world—from Australia, Canada, Europe, Japan, China—they're all recognizing islets as micro-organs and there are plenty of scientific papers describing the complexity of the islet micro-organ. For some reason, the FDA classified 2 decades ago, islet transplant as advanced cell therapy, like a cellular transplant. And they try to fit islet regulation with those of drugs or pharmaceutical company, which has been killing the field in the United States while the rest of the world is leaving us in the dust. Luckily for them and their patients, they can continue to perform islet transplant.
In the United States, unfortunately, we are near extinction of the field of islet transplantation. From over 150 transplants a year performed 2 decades ago, at the time of the clinical islet transplantation consortium of NIH [National Institutes of Health] phase 3 trial, now we have a handful—less than 5 transplants performed last year in the entire United States. So while Canada is celebrating, going to close to 1000 islet transplants, and they can continue to perform them on the patients in Canada, the United States are sort of blocked by this outdated regulation, that is not only an outdated regulation for classifying islets as a cell transplant and as an advanced cell therapy, but they're also dated in the inclusion and exclusion criteria. Because we're still using criteria that were set up 20 years ago, based on severe hypoglycemic episodes requiring hospitalization. And it's something that is virtually very difficult to observe now with the modern technology of the time, with the low glucose suspend alarm that can inform patients when they have a severe hypoglycemic episode.
This doesn't mean that these are not patients that require special attention, that are at higher risk of complication, because you don't have to end up in the hospital or requiring assistance from someone else to be exposed to this glycemic variability that is what is associated also with some of the worst risks of progression of complications in diabetes. I think that also in the inclusion/exclusion criteria, there will be a need to modernize the approach of regulatory agencies and require less strict criteria and base it more on normalizing glucose levels and glycemic variability, as Europe has been showing in the randomized trial between intensive insulin treatment and islet transplantation, where the timing of range is over 90% or 95% following an islet transplant. Even with the most modern artificial pancreas or insulin pump, that's a target difficult to achieve.
I hope there will be an expert panel reviewing also the criteria of inclusion/exclusion for islet transplantation, and hopefully, someone at the FDA will finally realize the mistake of classifying islets as advanced cell products and that will allow us to serve our patients in the United States as well.