Last September, Nature predicted a stem-cell showdown in Texas, between the US Food and Drug Administration (FDA) and a company providing unproven stem-cell treatments, and that seems to be happening.
In a severe “warning letter” posted on the agency’s website this week (but dated 24 September 2012), the FDA told Celltex Therapeutics of Sugar Land, Texas, that its stem-cell products fall under FDA regulation and need to be approved before use in patients. The company lacks such approval but has been providing them to physicians who then inject them to paying patients for pricey, unproven clinical treatments.
The FDA’s reasoning is that Celltex stem-cell preparations constitute drugs and do not meet the exemption requirements that would allow such cellular products to be used at the discretion of doctors. The FDA argues that the cells are more than “minimally manipulated” because the “processing … alters the original relevant characteristics of the adipose tissue” from which the cells were derived. The warning letter also states that injection of the cells does not meet the exemption requirement that they be applied for “homologous” use. (Although the explanation in the document is redacted, this is presumably because cells, originally part of adipose or fat tissue, are being injected for treatment of neurological and other non-homologous uses.)
Altogether the letter points to 29 “significant objectionable conditions” with Celltex’ operations, including the failure to ensure that procedures for guaranteeing safe and quality cells are being followed. The letter points out that Celltex has failed, in response to a previous chiding about quality-control procedures, to “provide sufficient detail to fully assess the adequacy of your corrective actions”.
The letter is a challenge to new regulations that the Texas Medical Board put in place in April, which had made FDA approval an option, not a requirement. Those regulations state that doctors injecting stem cells into patients need FDA approval or the approval of a local institutional review board (IRB). The warning letter makes clear that the FDA expects its approval to be mandatory — effectively replacing the “or” with an “and”.
The FDA, which also oversees IRBs, likewise blasted the Houston-based Texas Applied Biotechnology Research Review Committee (TABS RRC) IRB that approved a clinical study by Celltex. The FDA found that the IRB “significantly violated applicable federal regulations governing the operation and responsibilities governing the operation and responsibilities of IRBs”. The five faults detailed by the agency include a conflict of interest of two IRB members who had helped Celltex draft the study’s protocols and the failure to ensure that Celltex protocols met safety regulations designed to protect children. The FDA’s 24 September warning letter to TABS RRC says, “we have no assurance that the IRB procedures are adequately protecting the rights and welfare of the human subjects of research”. The warning letter forbids TABS RRC from enrolling any new subjects in studies until the “FDA has evidence of adequate corrective actions”.
FDA warning letters have teeth. Celltex had 15 days to detail steps taken to correct the various violations or risk “regulatory action without further notice” which could include “seizure and/or injunction”.
So what’s next for Celltex? According to an exchange that Paul Knoepfler had with Celltex, they are still in business.
On 1 October, a week after receiving the warning letter, Celltex attempted to defuse the news by announcing that it had received “a letter” (although Cellex didn’t reveal at that time that it was the relatively harsh “warning letter”). Noting disagreement with the FDA’s ruling that its processed cells need to be regulated as drugs, the company announced a “new clinical program” through which it planned to work with the FDA.
So perhaps within 15 days of 24 September, the company posted a letter that appeased the FDA. Even if it hadn’t, and the FDA has decided on some form of enforcement, we will not know until the agency makes its move.
Celltex could try to argue in court that the FDA does not have jurisdiction over unproven stem-cell treatments. But that has been tried, by Broomfield, Colorado-based Regenerative Sciences. That case upheld the FDA’s authority.
With Governor Rick Perry a big fan of stem-cell treatments — and the first publicized case of someone getting treatment there — there has been some speculation that he would stand up for Celltex.
But according to a spokeswoman for Perry, the governor says the matter is “between Celltex and the FDA“.