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Sept. 9 — Keeping up with the rapidly advancing science and finding sufficient financing are the main barriers to moving human cell and tissue products from the laboratory to use in patients, workshop participants said Sept. 8.
“Scientific evidence is crucial for the development of human cell, tissue and cell and tissue-based products (HCT/Ps),” Stephen R. Bauer, chief of the cellular and tissues therapy branch at the Food and Drug Administration’s Center for Biologics Evaluation and Research (CBER), told the FDA workshop in White Oak, Md.
“The current science allows the development of complex novel products,” he said, “but the science continues to evolve. It's a challenge to all of us, but we must follow the target.”
According to RTI Surgical Inc., HCT/Ps are used in more than a million medical and dental procedures each year, including wound care management, hernia repair, orthopedic and sports medicine procedures and bone and gum grafting and repair. But, according to workshop panelists, Big Pharma financial support for newly developing HCT/P therapies can be hard to come by.
Bauer noted at the workshop, titled “Scientific Evidence in Development of HCT/Ps Subject to Premarket Approval,” that the FDA's regulatory framework for HCT/Ps is tiered and risk-based and is focused on human cells or tissues that are intended for implantation, infusion or transfer.
Not all HCT/Ps require FDA premarket approval, Bauer said, and the workshop focused on those that do, which are higher risk and include allogeneic unrelated cord blood, autologous tumor vaccines and CAR-T cells. Allogeneic means tissues or cells that are genetically dissimilar and therefore immunologically incompatible, and autologous means cells or tissue obtained from the same individual.
Illustrating the challenges facing HCT/P research, Bauer discussed the FDA's MSC Consortium, in which seven agency laboratories studied MSCs derived from the bone marrow of eight human donors. “We concluded that cell surface markers do not inform us about MSC biological differences, and we demonstrated that MSC markers do not correlate with functional heterogeneity,” referring to the specific different tissue types into which the cells can develop. “We did, however, develop assays, the potential application of which may help us identify differences between MSC samples,” he said.
Irving Weissman, who co-directs the Stanford Institute for Stem Cell Biology and Regenerative Medicine, said a lack of financial support from industry has prevented advancement of promising cell and tissue technologies.
“The stakes are high,” Weissman said. “We have done things that should have been moved far forward, and the FDA wasn't our barrier, it was our partner. Unless we solve the fundamental problem of funding clinical translation, I don't see how we are going to progress with this so that it happens while we are all alive to see it.”
Weissman described how in 1987 he launched a Palo Alto, Calif.-based company, Systemix, to commercialize a unique method to isolate, purify and transplant blood-forming stem cells that could generate red cells, white cells and platelets. The idea was to put these cells to work to regenerate blood-forming systems in patients with aggressive cancers after they've undergone high-dose chemotherapy.
Weissman said he sold a majority share of Systemix in 1991 to Switzerland-based Sandoz Pharma, which became Novartis, which canceled its stem cell program in 2000. Novartis said at the time that it ended the program because it couldn’t produce blood stem cells in large enough numbers to develop a commercial market and that it wasn't in the business of producing personalized “custom-made” therapies.
Weissman said he later convinced Novartis to license key technologies to his new company, and a clinical study is ongoing at Stanford.
He told Bloomberg BNA at the workshop that the decisions of Big Pharmas will always be influenced by their bottom lines. As such, he said, “I believe that this type of research must be done by nonprofits because large biopharmas ultimately have other interests.”
Sixteen years after the decision to cancel its stem cell program, Novartis is a member of the Personalized Medicine Coalition and its website features articles on stem cells and regenerative medicine. A Novartis spokesman didn't immediately respond to a Bloomberg BNA e-mail request for comment.
Jacques Galipeau, director of the advanced cell therapy program at the University of Wisconsin at Madison, discussed his attempts to discover why positive results of animal studies on a particular mesenchymal stem cell (MSC) therapy aren't being duplicated in human studies.
Galipeau said that MSCs are useful in cell therapy because scientists can quickly generate therapeutic quantities of autologous MSCs from a 20-cubic-centimeter sample of bone marrow. He said MSCs have been found to be beneficial in mouse studies.
Generally, he said that scientific data using animals almost always show the positive effective of a therapy. He said the cells and tissue used in such studies are usually autologous and are from 100 percent fresh, viable MSCs taken directly from culture.
For human clinical trials, Galipeau said, nearly 100 percent of industry studies use allogeneic MSCs and 95 percent of studies use frozen, cryobanked MSCs that are thawed when needed for research. “Thawed MSCs display decreased immunosuppressive properties. This leads to the maxim: ‘MSCs are like sushi. Fresh is best.' ”
He added, “Convenience does not trump potency when missing efficacy endpoints in pivotal clinical trials.”
The last half of the workshop focused on presentations concerning injuries that have occurred as a result of unauthorized stem cell procedures and tumors that have developed as a result of stem cell injections.
Brian Mansfield, deputy chief research officer for the Foundation Fighting Blindness, said the foundation “believes in the promise of stem cell therapy” but also advocates that all clinical stem cell therapy should have convincing preclinical data for safety and efficacy and FDA authorization.
Panelists said that those promoting unauthorized procedures are playing on the despair of people whose doctors have told them they are going blind or that their cancer is spreading, for example, and there is nothing that can be done.
Weissman said there must be oversight of stem cell therapies. “But I hope these stories don't scare people off from the authorized therapies—because this area is hot.”
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