A couple of weeks ago, University of Minnesota professor Leigh Turner heard that the U.S. Food and Drug Administration (FDA) had paid a visit to Celltex, a Texas company that banks and manipulates stem cells. He dashed off a Freedom of Information Act (FOIA) request to the FDA, asking for pertinent records.

Leigh Turner

Bioethicist Turner had reason to be more than a little curious. In February he wrote to the FDA asking the agency to investigate Celltex, the operator of the nation’s largest stem-cell bank, to determine whether it was illegally administering unproven treatments.

Both barrels blazing, Celltex fired back, among other things demanding that the U of M muzzle Turner and threatening to sue a handful of critics. As stem-cell researchers and other bioethicists got involved, the controversy has only gotten hotter.

Turner knew, of course, that FOIA requests are known to  languish for months, if not years. And so he was stunned to get two quick replies from the FDA in June, one assuring him his request was being processed, followed nearly immediately by another explaining that the document he was to be sent was being redacted.

79 deficiencies detailed

Last week Turner received a nine-page “483 report” on an FDA inspection visit to Celltex headquarters from April 16-27. In the document, the agency draws the company’s attention to 79 specific violations involving basic manufacturing processes ranging from the lack of a sink where lab workers can wash their hands to labeling protocols that do not guarantee patients are being injected with their own cells.

In addition to concerns in 14 areas about documentation and validation, the agency said the cells destined for injection into patients can’t be assured to be sterile or to contain a specific type or number of living cells.

“One bottle had contradicting labels in English and Korean — probably indicating a quality-control problem in integrating reagents from RNL Bio, based in Seoul,” noted the journal Nature. “RNL Bio, which offers its own controversial stem-cell treatments and has been investigated after the death of two patients, licenses its stem-cell manufacturing technology to Celltex.”

Reaction from researchers and bioethicists elsewhere was swift.

‘A major setback’

“The report and the concerns it raises are also a big challenge for the adult stem cell industry more generally,” noted Paul Knoepfler, a leading stem cell researcher at the University of California Davis. “In fact, I view it as a major setback to the adult stem cell for-profit industry as a whole.”

For its part, Celltex issued a statement saying it had invited the agency to visit and had resolved most of its complaints. “Celltex continues to provide stem cell banking and multiplication services without interruption and has not received any disciplinary action from the FDA,” it said.

The function of adult stem cells is to replenish a body’s dying cells. They have shown promise for treating numerous diseases, including cancer, but are generally considered too experimental for widespread use outside of clinical trials.

Stem-cell clinics have sprung up anyway. Some send patients overseas. Others argue that adult stem cells are patient tissue and not drugs and thus not subject to FDA oversight. Celltex has argued that it does not treat patients, but rather banks their cells for use by their physicians.

According to the explanation in a March story in Nature, physicians remove from a patient five grams of abdominal fat, which are cultured by Celltex until they generate about 800 million cells. Patients, including sufferers of multiple sclerosis and Parkinson’s, then receive three injections containing at least 200 million cells apiece. According to one doctor interviewed by Nature, patients pay Celltex $7,000 per injection while their doctors receive $500 per shot from the company.

Most famous recipient: Gov. Rick Perry

Celltex’s most famous adult-stem-cell recipient is Texas Gov. Rick Perry, who was injected with his own stem cells to treat back pain. Perry later pushed a bill making the company the only state-approved stem-cell bank and led the Texas Medical Board to institute rules allowing the therapy to go ahead.

To Turner, the violations are only part of what makes the FDA documents significant. To him, the agency’s approach suggests it may not be done with Celltex. Most important, the agency classified Celltex as a biological drug manufacturer.

Drug manufacturers are required to apply for approval of new drugs they wish to market and to conduct clinical trials to show the drugs are safe and efficacious. And they need approval to go forth with the trials.

Expecting another shoe to drop

“This would be a serious blow to the business model of the company, which has argued to the FDA that it simply banks and processes stem cells ‘at the behest of independent physicians who diagnose and prescribe to their patients,’ without submitting its products to the FDA for approval,” explains Turner’s U of M colleague Carl Elliott, subject of his own spate of Celltex-related headlines and author of a weekly column in the Chronicle of Higher Education. “If the FDA demands evidence that adult stem cells actually work for the illnesses they are being used to treat, Celltex will have an uphill battle ahead.”

So what happens next? Turner and others are waiting to see if that shoe is an FDA warning letter, which could be the start of a sequence of events ranging from censure to closure.

“For the time being,” Nature reported, “the FDA seems to be approaching Celltex just as a stem-cell manufacturer — the observation form calls it a ‘biological drug manufacturer.’ But the clinical use is a separate problem. Another shoe is yet to drop.”