WIKIMEDIA, RYDDRAGYNMany of the stem cell lines used by academics and registered with the U.S. National Institutes of Health (NIH) would not be eligible for commercialization because they don’t pass muster with the Food and Drug Administration (FDA), according to a report published today (February 6) in Cell Stem Cell. The lack of harmonization between the agencies’ standards throws up a potential roadblack on the path from the laboratory to the clinic.
“The main concern is: How do we move this technology [to the clinic]? How do we translate it?” said Erica Jonlin, the author of the report and the regulatory manager at the University of Washington Institute for Stem Cell and Regenerative Medicine.
As of today, the NIH registry contains 261 stem cell lines eligible for federal research funding. As Jonlin pointed out in her report, each line had to pass ethical standards—namely, that the embryo donors consented for their use in research and that the embryos were created for the sole purpose of fertility treatment.
Some of the lines clearly state that they are not to be developed for therapies, but for the others that don’t have such restrictions, the point might be moot. That’s because the FDA’s guidelines for using human-derived products require that donors be screened for a number of diseases. “I can say most assuredly that most of the originating donors did not undergo the screening because it was never required,” Jonlin told The Scientist.
The result is a mismatch between what the two agencies require for stem cell research on the one side and therapeutic development on the other. “This shouldn’t be a surprise to anyone,” said Joy Cavagnaro, the president of Access BIO, a regulatory and preclinical services consulting group. She pointed out that the FDA’s expectations were first proposed a decade ago. “I just don’t think people think about [commercialization] while they’re doing research until, ‘Whoa, we could be close.’ And now it’s an issue.”
Getting stem cell lines to comply with FDA’s expectations would mean testing parents at fertility treatment centers for diseases. “To have them undergo testing is a gargantuan task,” Jonlin said. “I personally think it’s ethically unacceptable. And I can’t see how an institutional review board would approve that.”
The NIH did not respond to requests for comment. Although the FDA declined an interview, Paul Richards, a spokesman for the agency, said in an e-mail that “FDA is aware of the differences between our regulations and the NIH regulations.”
The ideal compromise, to Jonlin’s mind, is to test the cell lines themselves, rather than the donors, although this approach also presents challenges. For one, it’s costly. Tennielle Ludwig, the director of distribution, media optimization, and core service at WiCell Research Institute, said the cost to perform the disease screens the FDA asks for is between $85,000 and $250,000. “It’s a lot, but [even that] doesn’t in and of itself meet the FDA . . . requirements,” Ludwig said, largely because the FDA requires that donors be screened.
But all hope is not lost for stem cell lines that don’t meet the FDA’s expectations. It’s possible that the agency might make exceptions to its rules. Jonlin wrote in her article that the FDA has allowed products from inadequately screened lines to make it into humans—such as in the case of clinical trials from the company Geron. “The only way to know what the FDA would or wouldn’t do is file an IND [Investigational New Drug application]. Geron did that and H1 [stem cell line] went through,” said Ludwig.
Cavagnaro said the onus is on researchers and the industry to propose standards for testing stem cell lines. “What would be the appropriate standards when you don’t have this information? That’s what you put forward,” she said. “This is risk mitigation.”
Ludwig said Jonlin’s report is an important reminder for scientists who hope to have therapies on the horizon. “As a researcher, if you are intending to develop a cell therapy and you want to use your preclinical cell line, you have to be careful about your cell line.”
Not all existing stem cell lines are ineligible. Geoff Lomax, the senior officer for medical and ethical standards at the California Institute for Regenerative Medicine (CIRM), said that one of his organization’s grantees has derived a stem cell line in compliance with federal recommendations. “Because of our ability to provide funding for that process, it hasn’t impacted the development of this product,” Lomax told The Scientist. But he adds, “if there isn’t funding to sort all that out, it’s hard to see how it can happen.”
E.C. Jonlin, “Differing standards for the NIH Stem Cell Registry and FDA approval render most federally funded hESC lines unsuitable for clinical use,” Cell Stem Cell, 14:139-40, 2014.