Pure and Simple-Islet Center First to Receive FDA Certification

By 2004, every islet transplantation facility will have to be certified as a Good Manufacturing Practice (GMP) facility by the U.S. Food and Drug Administration (FDA). The Islet and Cellular Transplantation Center at the University of California, San Francisco (UCSF) is the first such facility to receive GMP certification – ensuring that the highest international standards are maintained for the isolation and purification of islets for transplantation.

On July 18, 2002, DIABETES HEALTH was given an exclusive tour of the center – which the FDA has now locked down to the public for sterility. Jeffrey Bluestone, PhD, director of the Diabetes Center at UCSF and co-director of the UCSF Islet Transplantation Program, hosted the tour.

Purifying Islets and Discovering New Sources

The 4,500-square-foot, $4.5 million facility occupies the top floor of the six-story UCSF Mission Center, located southwest of downtown San Francisco. The center will focus on purifying islets to prepare them for transplantation at the UCSF Parnassus campus across town.

In addition, medical workers at the new center will be evaluating new anti-rejection drugs developed at other UCSF facilities that will be taken by people who receive islet transplants. Historically, according to Peter Stock, MD, associate professor of surgery and co-director of the Islet Transplantation Program at UCSF, islet transplants have failed not because the concept is incorrect but because of rejection.

“This facility can really focus on getting the islets to the recipient and then developing a strategy for preventing rejection,” says Stock. “This will set the stage for the future because as we figure out new sources for islets – and figuring that out is part of this facility as well – ultimately we will be able to get more aggressive in helping many more people with diabetes.”

Some of the new “sources” of which Bluestone and Stock speak include using adult stem cells to manufacture new islets as well as employing gene therapy.

“I think the critical problem we are going to run into soon is the shortage of pancreases,” predicts Bluestone. “There are about 3,000 to 4,000 pancreases available each year. We are not going to solve any problems with this current supply. Therefore, this center will also focus on discovering ways to increase islet supply.”

Starting Dirty, Ending Clean

During our tour, Bluestone explained that the space was built to maximize the notion of “starting dirty and ending up clean.”

“You are starting out with a pancreas that has been in some other city that is flown in here under the best of sterile conditions,” he describes. “What we need is to come out the other end with a small population of islets that we can inject into someone and feel confident that they are functional and sterile. That is what the FDA wants to have.”

The first rooms in the facility are the quarantine rooms, where a set of test materials arrives from the outside. Then, as you move into a more sterile prep room, the air changes and becomes purer. This is accomplished through the filters in the ceiling, which change the air 40 times an hour.

“In the real world, there are 100,000 particles of dust per cubic square foot,” says Bluestone. “In this room, there are 10,000 particles of dust per cubic square foot. This is important because this is where we will unwrap the pancreas and remove all of the outside real-world material and put it into a sterile container, which will then be sent through the door to the next room.”

In the next room, the number of particles of dust per cubic square foot decreases even further, from 10,000 to 100. It is here where the transplant team unwraps everything.

“It is totally sterile in here,” Bluestone continues. “If you go to the roof of the building, you can see all of the duct work and air handling that comes from the whole building. There are eight air-handling units on the roof. Five of the eight handle our facility on the sixth floor. And one out of those five handles just this small room, to make it sterile. In addition, computers and alarm systems make sure the air flow is always correct.”

In this “islet preparation suite,” the UCSF team puts the islets in an incubator to culture for two days – unlike the Edmonton Protocol procedure, which does not include this culture time.

During those two days, “we are already starting the transplant recipient on anti-rejection drugs in preparation for the transplantation,” Bluestone notes, adding that by doing this, they can reverse diabetes with one transplant in the majority of patients. The Edmonton Protocol procedure requires two transplants.

After the islets are isolated, they are then put into a sterile bag, double-wrapped and sent to a surgical suite at the UCSF Parnassus campus. Contamination of the islets while in transit is not a problem, Bluestone asserts.

“The islets will be tested before going into the patient. There have been 120 islet transplants done in the past two years, and contamination has not been a problem. The Edmonton Protocol procedure doesn’t culture their islets, and there hasn’t been an incidence of contamination.”

Rooms of the Future

Next Bluestone took us to what they’re calling the “rooms of the future” – the first of which is intended for future work on gene therapy.

Bluestone describes gene therapy as “the ability to take genes from people that have a biologic activity and introduce them in other people. For instance, if we had a gene that could make islets grow, we could put that gene into the islets that we make here and grow up the islets; [we could] make 100 times more islets than we had to begin with and use those for transplantation.”

He adds that gene therapy, although slow to develop as a concept, is still an important adjunct therapy that will be used more and more.

“And islet transplantation is just a great place to do it.”

The last room on the tour was the stem cell room. Here the UCSF staff will one day develop and grow new islets from the pancreas and other tissues.

“We will also harvest bone marrow in this room, because bone marrow may be one of the tissues we can use to alter the immune response,” says Bluestone. “There is more and more evidence that, since your own immune system comes from your bone marrow, if we can put the marrow from the donor of the pancreas in with the transplanted pancreas, we might be able to modify the immune system.”

Brother, Can You Spare $150,000?

Bluestone says the current immunosuppressive drugs used to prevent rejection of the islets carry many unknown risks that make islet transplantation suitable only for those who have few other options for controlling their glucose levels.

He adds that an islet transplant itself costs between $125,000 and $150,000.

“One of our primary goals is to get islet transplantation insurance reimbursable,” he says, adding that in the future there will probably be attempts to commercialize islet transplantations. “It would be great if we could do this for people in California and then pass it on to them without breaking the bank.”

Leave a Reply

Your email address will not be published. Required fields are marked *

Time limit is exhausted. Please reload CAPTCHA.