The US Food and Drug Administration (FDA) is continuing to enforce a controversial policy involving the regulation of stem cell therapies, which the agency defends as enforcing established authority but critics have derided as the regulation of the practice of medicine.
A 24 September warning letter to Texas-based CellTex Therapeutics Corporation references the firm's use of adipose tissue (lipoaspirate) recovered from donors, which is then isolated and cultured into adipose mesenchymal stem cells (AdMSC) before being administered to patients. In the case of CellTex, its patients primarily sought treatment through clinical trials the company runs.
As with other stem cell therapies, FDA contends the company's manipulation of stem cells exceeds the agency's rules on minimal manipulation, and thus falls under the human cell, tissue or cellular and tissue-based product (HCT/P) regulations of 21 CFR 1271, which the company failed to meet by failing to obtain approval from FDA for its stem cell product.
Sterile Processing Deficiencies
More substantively, FDA alleges the company had a number of deficiencies related to its current good manufacturing practices, including invalidated autoclave sterilization and other aseptic processes, failure to meet bacterial and fungal limits for some parts of its manufacturing processes and failure to conduct a cavalcade of other quality operations.
FDA's warning letter comes after a Form 483 was sent to CellTex in April 2012 after an inspection by FDA that same month. Five subsequent letters sent to FDA by the company failed to assuage the agency's concerns, it said. "We have concluded that your responses did not provide sufficient detail to fully assess the adequacy of your corrective actions." FDA said it was requesting prompt action, particularly in regard to drugs that have already been manufactured at the company's Sugar Land, TX facility.
The agency's concerns, particularly about not meeting standards for sterile manufacturing, could be seen as more serious after an outbreak of fungal meningitis has sickened hundreds and killed more than 15 people. The infection was spread by injections-the same method CellTex uses to reintroduce stem cells into a patient-contaminated with the fungus.
Controversial Authority and an IRB
But the agency's inspection is also steeped in controversy. In April, Texas made headlines by allowing doctors at clinics like CellTex to conduct clinical trials on patients using their own stem cells so long as the procedure received approval from an Institutional Review Board (IRB). The move set up the possibility of a showdown with FDA by establishing two competing authorities: the Texas Medical Board, which says it regulates the procedures, and FDA, which claims the procedure is in fact an unapproved biological product.
The IRB that approved CellTex's procedures, Texas Applied Biomedical Services, was also the subject of a warning letter sent the same day as CellTex's.
Though FDA did not cite the IRB for any activities related to its approval of CellTex's products specifically, it did note a broad range of deficiencies-lack of documentation, undeclared conflicts of interest, non-compliant pediatric studies and unqualified members-and said FDA would place a hold on all new studies and existing studies overseen by the IRB.
FDA Playing Hardball?
The warning letter and actions could be seen as some as an aggressive move against both CellTex and the stem cell industry at large. Few-if any-warning letters sent by FDA have simultaneously targeted both a company and its IRB.
But FDA may also be looking to bolster its authority in the wake of the decisions by the Texas Medical Board. Its legal authority has since been reinforced by a July 2012 DC District Court decision in which the court affirmed FDA's authority to regulate stem cell therapies as drug products. That case, however, remains on appeal and it may be years before a final decision is rendered.
In the meantime, some critics, including former FDA Associate Commissioner Scott Gottlieb, say the use of this authority is unwarranted. Writing in the Wall Street Journal in August 2012 along with legal expert Coleen Klasmeier of Sidley Austin LLP, Gottlieb argued the collection and injection of stem cells into a patient is the practice of medicine-not a drug.
"The constraint that a drug needed to be a 'thing' has been read out of the law by FDA, and the district court appears to have accepted that position," he wrote, referring to US V. Regenerative Sciences, the July 2012 court case.
"If the FDA's victory is upheld on appeal, then conceivably nothing done as part of clinical practice is beyond the agency's reach … there may be little to prevent the FDA from imposing its drug-approval requirements on any cell-based procedure."