FDA Bashes Stem Cell Firm for Violations

FDA Bashes Stem Cell Firm for Violations

June 28th, 2012 // 10:06 am @ jmpickett

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Four months ago, a bioethics professor at the University of Minnesota asked the FDA to investigate a stem cell company called Celltex Therapeutics, which has ties to a controversial stem cell company in South Korea called RNL BIO, over concerns about patient-client safety, the quality of scientific research supporting their proposed business model and whether both will conform to relevant federal and state laws and regulations (read the letter here).

The letter from Leigh Turner came amid a confusing dust-up surrounding the employment status of one former Celltex executive, which triggered scrutiny of the relationship between Celltex and RNL. On his blog and in his letter to the FDA, Turner had also written that the two companies planned to bank and administer stem cells, citing various reports as well as an agreement in which RNL was called BioLife Stem Cell at the time (read here).

Celltex, however, disputed his assertions and wrote the University of Minnesota and the FDA to say that Turner mischaracterized its activities (back story). The university responded by saying that Turner spoke only for himself, but is protected by school policies on academic freedom, which he regarded as vindication. Now, Turner has been vindicated again.

After inspecting Celltex facilites in Sugarland, Texas, this past April, the FDA found dozens of safety violations and was unable to ensure that the stem cells were alive when used to treat patients, according to a 483 inspection report. A former FDA official tells The Houston Chronicle that the problems – 79 deficiencies that ran from incorrectly labeled products to failed sterility tests – are so serious Celltex could be shut down if a resolution is not found quickly (here is the 483 report).

In a statement given the paper, Celltex ceo David Eller downplayed the findings, saying the company invited the inspection. “As you can see from the agency’s constructive observations, we shared proprietary information on all aspects of our laboratory operations,” Eller wrote. “The FDA is already aware we have resolved many of its observations and we are working to address the remainder.” He added that Celltex has continued to provide “stem cell banking and expansion services” without interruption after the FDA visit, according to the paper.

As for Turner, he wrote us this: “I’m astonished both by the number of observations made by FDA investigators during their inspection of Celltex and by particular observations. When I contacted the FDA in February, I was concerned that Celltex reportedly was charging patients for access to clinically unproven stem cells. I didn’t address specific features of the laboratory in which Celltex processes, expands, and banks mesenchymal stem cells. The 483 addresses some of the concerns that prompted me to write to the FDA, though let me add that there is no reason to assume that my letter prompted this inspection. The 483 also identifies many fundamental problems with Celltex’s manufacturing facility; these observations go far beyond the issues I outlined…

“One of the most significant points in the 483 is that Celltex is classified as a Biological Drug Manufacturer. This label is important because it indicates that FDA regards Celltex as engaged in manufacture of mesenchymal stem cells —biological drugs — rather than providing access to minimally manipulated stem cells. The list of twelve supplies and reagents used during manufacture of mesenchymal stem cells also suggests that FDA will not agree with Celltex’s claim that it is engaged in ‘minimal manipulation’ of stem cells.

“In addition to these key points, the 483 contains such surprising observations as: Celltex does not perform a process validation for manufacturing MSC’s ‘to assure batch uniformity and integrity as related to each of the following finished product characteristics: viability of cells, the specified cell count, cell type, and appearance of cells;’ it does not validate ‘banking and thawing process to assure viability of MSC’s;’ ‘procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not established, written, and followed;’ some ‘MSCs failed initial and repeat testing for sterility”; laboratory equipment is improperly located;’ and MSC’s ‘made available for distribution were not labeled accurately.’ One observation in the 483 notes that a Certificate of Analysis reviewed by the Investigators stated, ‘FOR RESEARCH USE ONLY. CAUTION: Not intended for human or animal diagnostic or therapeutic uses.’

“I find it remarkable that stem cells from this manufacturing facility are available for commercial distribution to individuals with multiple sclerosis and Parkinson’s disease. I’m deeply concerned about the safety, health and personal savings of persons receiving these cells. I worry that in addition to paying $20,000 to $30,000 for stem cells that have not be subjected to proper evaluation within clinical trials, could harm them, and provide no assurance of benefit, they are being exposed to risks that are avoidable if good manufacturing practices are followed.

“I hope Celltex soon receives a warning letter from FDA and the company is compelled to stop distributing stem cells to patients. Celltex should not be allowed to resume manufacturing and distributing mesenchymal stem cells until the manufacturing facility operates according to good manufacturing practices, and the company complies with all applicable federal and state regulations (including submission to FDA of an Investigational New Drug application), ethical and legal protections for research participants, and good clinical research practices. Based upon Celltex’s performance to date, there is reason to question whether the company will ever meet these standards.”

Among Celltex patients, by the way, is Texas Governor Rick Perry, who received stem-cell injections last summer for back pain and has tried to make the state a stem cell center. Celltex co-founder Eller is also a Perry backer. In April, the Texas Medical Board approved rules regulating the therapy, which isn’t approved by the FDA. The rules allow doctors to use stem cells as long as they get the approval of a review board that evaluates clinical research for safety. The board members were all appointed by Perry