The differences in how regulatory agencies regulate medical products can result in disparities in product availability, as has been the case with pancreatic islet cell therapy.
US FDA regulates pancreatic islet cell transplantation as a biologic drug for allogeneic use while Europe, Canada, Australia and Japan regulate islets as a tissue or organ.
Experts discussed the impact of these different approaches at the Center of Excellence in Regulatory Science and Innovation (CERSI) summit held in San Franciso on 7 January. They spoke on a panel addressing how regulators can work together to make medical products commercially viable and available worldwide.
Peter Stock, co-director of the Pancreatic Islet Cell Transplantation Program at the University of California, San Francisco, noted that transplantation of beta cells, either as a whole organ pancreas or as islet cells, results in states of insulin independence. Both the organ and cells are derived from deceased donor organs. He said islet transplantation is a safer and simpler procedure.
Stock said pancreas transplantation is performed about 1,000 times a year in the US, usually in conjunction with a kidney transplant. He noted that since the procedure has cardiovascular stressors, the vast majority of people with diabetes cannot benefit from it.
He commented that given the degree of manipulation involved in islet transplantation it makes sense that it is regulated by the FDA. On the other hand, he said, islets are in essence mini organs containing a network of vessels, nerves and multiple endocrine producing cells, so it also makes sense that they should be regulated by the same structure that’s in place for solid organ transplantation.
“So the consequences in the United States [are that] allo islet transplantation is not available at almost every transplant center and only one private company affiliated with an academic institution got a license, a BLA,” Stock said. “But in Europe, allo islet transplantation has been available to patients in transplant centers and safety and efficacy has been verified in over 1,000 patients.”
‘Discrimination’ In Lack Of Access
James Shapiro, professor of surgery, medicine and surgical oncology at the University of Alberta, noted that Health Canada approved islet cell transplantation in April 2001. “So, the FDA lags 23 years behind Canada on this issue. And as a result, Americans with severe labile diabetes are missing out on access to this therapy,” he said.
Shapiro said human islet transplants with minimal manipulation are clearly not drugs and the risk to recipients is low provided GMP manufacturing and final product release criteria are adhered to. “I think still we don’t have the regulation for this quite right in the US,” he stated.
Thierry Berney, emeritus professor of surgery at the University of Geneva School of Medicine, noted that in France and Switzerland, islet transplantation is considered standard of care for patients with complicated type 1 diabetes.
“There are a lot of patients who are unable to undergo whole pancreas transplant, mainly because they have cardiovascular issues that make them not fit for a pancreas transplant,” he said. And in this respect, “the lack of access to islet transplantation could be seen as some kind of discrimination when these patients are compared to the patients who are fit for pancreas transplantation.”
Probably Ways FDA ‘Can Do It Better’
Moderator Laura Esserman, professor of surgery and radiology at UCSF, asked Peter Marks, director of FDA’s Center for Biologics Evaluation and Research, who was in the audience, if this information could get the agency to reconsider the issue.
Marks replied that the FDA has acknowledged this is a very important procedure but under the agency’s regulations pancreatic islet transplantation is a drug.
“That's just how we define a drug, which is [if] it's more than minimally manipulated and an allogeneic product, it's a drug. And that said, there probably are ways that we can do it better,” he stated, noting that the agency simplified the situation for cord blood cell transplantation.
“We, I think, would like to work together to find ways to decrease regulatory burden, but to get to a place where we can ensure that the products that will get to people will be safe,” he stated. “So, I think there is some compromise here in the middle.”
FDA approved the first allogenic pancreas islet cell product, CellTrans, Inc.’s cellular therapy Lantidra (donislecel-jujn), last year. It is approved for treatment of adults with type 1 diabetes who are unable to approach target HbA1c because of current repeated episodes of severe hypoglycemia despite intensive diabetes management and education.
The agency approved the treatment based on clinical data from only 30 patients using the endpoint of insulin independence, which FDA deemed to be clinically meaningful. (Also see "CellTrans’ Lantidra: Type 1 Diabetes Cell Therapy Overcame The Odds On Nontraditional Path To Approval" - Pink Sheet, 12 September, 2023.)
