Public Meeting Reveals Weak Oversight of Xenotransplantation

FDA Official Admits Technology is “Fraught With Danger”

(New York) – A January 13th meeting of the Food and Drug Administration’s Xenotransplant Subcommittee in Gaithersburg, Maryland revealed that the FDA is ill-prepared to protect the public from infectious diseases that might result from animal-to-human organ, cell, and tissue transplants.

On the agenda, among other things, was a review of proposed guidelines to “indefinitely defer” blood and plasma donations from xenotransplant recipients and their “close contacts.”

“The mere fact that these guidelines are being proposed, demonstrates that xenotransplantation poses a threat to the public health, and that previous draft guidelines from 1996 - which also recommended blood bans from patients - are being ignored,” says Alix Fano, director of the Campaign for Responsible Transplantation (CRT), an international coalition of 80 public interest groups opposing xenotransplantation.

Dr. Phil Noguchi, Director of FDA’s Division of Cellular and Gene Therapies, acknowledged that xenotransplantation is “fraught with danger.” Yet he revealed that there are currently 12 FDA-approved xenotransplant clinical trials ongoing in the U.S.. Most, if not all, are industry-sponsored, and involve the use of pig cells to treat diabetes and neurological diseases, and whole pig livers and cells to perfuse the blood of patients with acute liver failure. In order to perform such trials, companies must submit an Investigational New Drug (IND) application. Yet Dr. Jay Siegel, Director of FDA’s Office of Therapeutics Research and Review asked, “Are there activities being done that are not under IND that should be? I would be shocked if there weren’ t.” Moreover, some companies don’t seem to be keeping track of their patients or performing government-mandated safety tests.

At the meeting, Genzyme, a Cambridge, Massachusetts-based biotech company, described how it had been treating about 100 burn patients per year since 1987 with a xenotransplant product called Epicel, oddly regulated as a device. The company uses 3T3 mouse cells to grow layers of human skin, which are then applied to the patient. The mouse cells are allegedly irradiated to prevent them, and any viruses, from proliferating; though when pressed at the meeting, Genzyme’s President admitted that the company was still assessing the efficacy of its irradiation method. Moreover, it had not performed FDA-required tests to determine whether its mouse cells could infect human cells in-vitro. Most shocking was the company’s admission that it had not kept a registry of the patients it treated, nor followed up to see whether any of them might have developed signs of illness or infection. Genzyme said it would be “impractical” to try to find these patients. The FDA seemed to have no knowledge of this situation.

FDA’s policies were revealed to be ill-defined and easily changeable. After hearing testimony from the blood industry, the Subcommittee voted to eliminate a key component of its blood guidelines published just two weeks earlier.

The ramifications of blood supplies contaminated with HIV, hepatitis B and C have been deadly. Recently, about 285,000 Americans and 25,000 Canadians, who spent 6 months or more in Britain since 1980, were barred from donating blood, for fear of Creutzfeldt Jakob “mad cow” Disease (CJD). Because it takes years, before symptoms of CJD appear in humans, authorities worry that potential blood donors may be carrying the disease without knowing it. The FDA’s blood guidelines do not consider that some pig viruses may lie dormant for decades, or may be spread like the common cold, leaving the blood supply vulnerable. Dr. Andrew Dayton of the FDA’s Division of Transfusion Transmitted Diseases, and architect of the guidelines, acknowledged that if a xenotransplant-related virus entered the blood supply by mistake, the results would be “disastrous” and the necessary withdrawal of contaminated blood products would cause serious blood shortages.

While some Subcommittee members seemed to downplay the threat of infection by pig viruses, virologist Jonathan Allan of the Southwest Foundation for Biomedical Research in Texas commented that, for FDA to recognize infectious disease risks in nonhuman primates, but not in pigs, is arbitrary. Dr. Prem Paul, a veterinary researcher at Iowa State University, warned that new pig viruses were continually being discovered; they had not been extensively studied; and the potential existed for them to mutate and infect humans. British veterinary pathologist David Onions concurred that “some human cells will likely be infected in a xenotransplant.” He cautioned that porcine parvovirus, which can change hosts, escape inactivation treatments, and which has already been found in Porcine Factor 8 - used to treat hemophiliacs - is of great concern.

A national name-based registry of all patients, dead or alive, who have received xenotransplants, as well as their close contacts, and relevant health care personnel, would provide the only hope for preventing blood donations from these individuals. Although such registries are plagued by problems - they are invasive of privacy and restrictive of liberty; their procedures cannot be legally enforced; they would be expensive to set up and manage; and will always be vulnerable to human error (i.e. if patients marry, change their names, relocate, or if hospital procedures are not carried out correctly) - the Centers for Disease Control has concluded that name-based registries provide the most reliable means for tracking infections like HIV. Although xenotransplantation could cause an AIDS-like epidemic, xenotransplant patient registries do not exist.

“In our view, the FDA’s xenotransplant policy is based on containment, rather then prevention of infectious diseases,” says CRT’s Fano. “Xenotransplantation is causing a mountain of problems and extra work for numerous branches and agencies of the federal government. We are concerned that the FDA has already failed to provide oversight for human tissues infected with HIV; it was cited for “weak oversight” of tracking and recall systems for defective medical devices and medical implants; and in 1996, it approved the use of a bioengineered plasma product that transmitted hepatitis A to hemophiliacs. We cannot afford any more public health disasters. If the FDA was truly interested in protecting the blood supply and the public health, it would ban xenotransplantation immediately,” says Fano.