The Centers for Disease Control and Prevention (CDC) recently released a report detailing serious infectious adverse events after injection of non–Food and Drug Administration (FDA)–approved stem cell products derived from umbilical cord blood. The report contains complication information on 12 patients in Texas (seven), Florida (four), and Arizona (one). Stem cell products derived from umbilical cord blood are FDA approved only for hematopoietic and immunologic reconstitution.^[1] The products in the CDC report, however, were used for non–FDA-approved conditions, such as osteoarthritis and pain, in orthopedic clinics, pain clinics, spine treatment clinics, and ambulatory surgery centers. The complications included bloodstream infections, joint infections, and epidural abscesses. All of the patients required hospitalization for 4 to 35 days, but no deaths were reported.^[2] All 12 patients had received products processed by Genetech, Inc., and distributed by Liveyon, LLC.

No validated process for sterilization currently exists, so the manufacture of stem cell products derived from umbilical cord blood needs to be strictly controlled. Companies often market their products as FDA registered, but this is not the same as an FDA-approved product.

Five different organisms were isolated from the patients, including Escherichia coli, Enterococcus faecalis, Proteus mirabilis, Citrobacter koseri, and Citrobacter freundii. Secondary to bacteria being found in unopened vials from clinics in Florida and Texas, investigators suggested it is less likely that the contamination occurred at the involved clinics. The CDC, therefore, reported that the contamination likely occurred prior to distribution.^[3] Furthermore, the tested unopened vials demonstrated contamination with similar organisms. They also found that all six of the unopened vials tested in Texas came from the same cordblood donor and had the same processing date as the vials that had been used in the patients who developed infections. (The seventh affected Texas patient received cells from a different donor.) Four other unopened vials tested in Florida were found to have different donors and processing dates than the vials in Texas. Two of the four vials came from the same donor and had the same processing date. Of those two vials, one was found to contain E. coli. The remaining two vials had different donors and different processing dates. One of those vials was found to be contaminated with E. coli and E. faecalis.^[2]

No validated process for sterilization currently exists, so the manufacture of stem cell products derived from umbilical cord blood needs to be strictly controlled.^[4] The Genetech-manufactured, Liveyon-distributed product is registered only with the FDA and is not approved by the FDA. Companies often market their products as FDA registered, but this is not the same as an FDA approved product. Many patients, as well as some providers, are unlikely to know this distinction, which may lead some to believe that the products have undergone an extensive FDA review process and obtained official FDA approval when, in fact, FDA-registered products are not subject to the same rigorous investigations.

Currently, several companies, clinics, and providers advertise stem cell treatments for non–FDA- approved indications for which no reliable or only weak evidence of efficacy or safety exist. The treatments are often not performed under standard-of-care infection control conditions, further increasing the risk of complication.^[5]

The recent CDC report demonstrates the potential risk of non–FDA-approved stem cell treatments.^[3] Per FDA recommendations, patients should avoid receiving these products outside of controlled clinical trials under an investigational new drug application.^[1] Any adverse events associated with the Genetech/ Liveyon products or any unapproved stem cell therapies need to be reported to FDA’s MedWatch Safety Information and Adverse Event Reporting Program. The ASRA Regenerative Medicine Interest Group is committed to continuing to inform our members of adverse events associated with regenerative medicine applications to pain medicine.

References

1. Guh AY, Thompson ND, Schaefer MK, Patel PR, Perz JF. Patient notification for bloodborne pathogen testing due to unsafe injection practices in the US health care settings, 2001–2011. Med Care 2012;50:785–791.
2. Perkins KM, Spoto S, Rankin DA, et al. Notes from the field: infections after receipt of bacterially contaminated umbilical cord blood–derived stem cell products for other than hematopoietic or immunologic reconstitution—United States, 2018. MMWR Morb Mortal Wkly Rep 2018;67:1397–1399.
3. Food and Drug Administration. FDA warns about stem cell therapies. 2017. Available at: https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm286155.htm. Accessed March 1, 2019.
4. Marks PW, Witten CM, Califf RM. Clarifying stem-cell therapy’s benefits and risks. N Engl J Med 2017;376:1007–1009.
5. Food and Drug Administration. Guidance for industry: biologics license applications for minimally manipulated, unrelated allogeneic placental/umbilical cord blood intended for hematopoietic and immunologic
   reconstitution in patients with disorders affecting the hematopoietic system. Available at: https://www.fda.gov/downloads/biologicsbloodvaccines/guidancecomplianceregulatoryinformation/guidances/cellularandgenetherapy/ucm357135.pdf. Accessed March 1, 2019.