FDA Advisory Committee Recommends
Ground Rules for Stem-Cell Products

Steve Mitchell

July 17, 2000; Washington, D.C. (Reuters Health Professionals) -- At a meeting on Friday, the US Food and Drug Administration's (FDA) Biological Response Modifiers Advisory Committee made several recommendations about how the FDA should proceed in regulating the development of stem-cell-based products. "We agree that there should be information available for any [stem] cells heading towards clinical trials that includes karyotyping, in vitro growth assays, contact inhibition...and animal models," Chair of the Committee Dr. Daniel R. Salomon of The Scripps Research Institute said in summing up the committee's position.

In addition, the committee agreed that the fate of the cells should be tracked in animal models after implantation to ensure that the cells differentiate into the phenotypes necessary to treat the disease at hand. The committee could not agree on specific markers that should be used, and indeed the FDA was uncertain on this issue as well. Dr. Malcolm Moos, medical officer in the FDA's Division of Cellular and Gene Therapies, commented to Reuters Health that it's too early to predict how many markers may be needed, saying, "I know of some cases in which 18 markers are not enough." He added, however, that one marker would be adequate, if it could be proven to be associated with long-term safety and efficacy. "We're concerned about ensuring that different lots" of stem cells are homogenous, which includes "controlling sources...training people...SOPs," Dr. Moos said. He noted that this is not different from other FDA-regulated products, but that it is more difficult with stem-cell-based products because "we don't know what to measure, we don't know what to control."

In a presentation to the committee, Dr. Moos said that "one of the things that triggers the FDA's concerns" is if the cells in question are "manipulated extensively." He added that "migration of stem cells also seems to be quite extensive." Dr. Moos commented, "We don't know if this is a problem...but we need input on that."

Dr. Jay P. Siegel, director of the FDA's Office of Therapeutics Research and Review, said, "Once you start treating people and you change your product, the critical thing is to know what you had and how it has been changed." He continued, "The most critical issue in Phase-I is dose escalation...I'm going to want to know...if you've tripled the dose three-fold," if the potency has gone up three times or has it gone up ten times. "If [investigators] can characterize something that's more efficacious and safe, we're likely to move forward on that," Dr. Phillip D. Noguchi, Director of the FDA's Division of Cellular and Gene Therapies, said.

As far as standards for screening donors for diseases and the issue of confidentiality, the Committee felt that the same standards used in blood banking and organ transplantation were appropriate for stem cell research. Most members were also in favor of screening the donor for certain genetic mutations that may predispose someone to disease, but they could not reach a consensus as to which mutations were the most important. Committee member Dr. Richard E. Champlin of the University of Texas MD Anderson Cancer Center noted that "with autologous applications...you'd have a shorter list of things you have to check."

The committee did not feel that any source of stem cells should be disallowed. Dr. Salomon said, "There isn't a sense [among the Committee members] that anything is off the table...As long as the source is well-characterized and fulfills all the other regulations...it isn't off the table." The Committee agreed that adult stem cells posed less of a risk of tumorigenicity than embryonic stem cells but that "any stem cell has to be tested by some standard of tumorigenicity," Dr. Salomon said. In regard to animal models, Dr. Solomon suggested that investigators "should start with some sort of model" that has been "validated by a working group of experts in the field." The rest of the Committee favored this approach.

Both Dr. Noguchi and Dr. Moos commented to Reuters Health that the agency is attempting to establish a set of general conditions that all stem cell products would be expected to meet. And from that, they would then proceed to more specific regulations or, perhaps, dealing with products on a case-by-case basis.

It may be important for the FDA to act quickly because according to Richard Garr, President and CEO of Neural Stem Biopharmaceutical, a company that produces stem cells and holds the patent to a technique of isolating stem cells, the field of stem cell research is evolving faster than most scientists realize because a lot of companies do not publish their research. "In the next [12 - 18] months," Garr said, "there will be companies coming to the FDA" that want to move forward with human clinical trials of stem cell products to treat neurological disorders.