Recently, the CDC announced to the public the existence of an outbreak of infected patients who had received a donor-derived regenerative therapy in several states: “Notes from the Field: Bloodstream and Joint Infections in Patients After Receiving Bacterially Contaminated Umbilical Cord Blood-derived Stem Cell Products for Non-hematopoietic Conditions — United States, 2018.” It isn’t a good thing when the CDC gets involved in detecting patterns of infectious disease cases in regenerative medical treatments, but fortunately they traced the cases back to a donor-derived product sold to physicians by Liveyon, LLC of Yorba Linda, CA, which instituted a nation-wide recall of their so-called regenerative products.
The FDA issued a Warning Letter to Genetech (San Diego, CA) on November 29, 2018, which was the supplier of the contaminated donor-derived therapy to Liveyon. I will cover the hair-raising details the FDA cited in their Warning Letter to Genetech, before I move on to the puzzling comments made by Liveyon’s CEO, Mr. Kosolcharoen, about the issue of Liveyon selling contaminated cord blood product and what they have done about the problem.
According to the FDA’s Warning Letter, Genetech collected amniotic fluid from women undergoing Caesarian section. Straight away, the FDA states the following:
…the Food and Drug Administration (FDA) documented that your firm processes human umbilical cord blood derived cellular products ReGen®5, ReGen®10, and ReGen®30 for allogeneic use (hereinafter, “umbilical cord blood products” or “products”) that you distribute to Liveyon LLC (Liveyon), located in Yorba Linda, CA. The umbilical cord blood products are administered via intra-articular injection and in some cases intravenously or “applied directly to the affected soft tissue.”
So, the FDA confirmed that cord blood-derived cell-containing products were being sold to Liveyon, LLC, which in turn sold them to physicians who injected the non-compliant products into patients via intra-articular, IV routes and “applied to affected soft tissue”. The FDA indicated that they reviewed the Liveyon website to determine the indications to which the Genetech products were being used for treatment.
The FDA stated that the products were being used for treatments that didn’t meet the standard for a homologous use:
…the umbilical cord blood products are intended to treat a variety of orthopedic conditions. Because the umbilical cord blood products are not intended to perform the same basic function or functions of umbilical cord blood in the recipient as in the donor, such as forming and replenishing the lymphohematopoietic system, using the umbilical cord blood products to treat orthopedic conditions is not homologous use…
Furthermore, in order to really drive home the point that cord blood-derived products shouldn’t be used willy-nilly with just any patient, the FDA highlighted what I frequently point out about most of the so-called miraculous goop products: if the cells are viable, a physician could be liable (for using an unapproved drug):
…the umbilical cord blood products fail to meet the criterion set forth in 21 CFR 1271.10(a)(4). Specifically, the products, manufactured from donated umbilical cord blood, are dependent on the metabolic activity of living cells for their primary function and are not for autologous use, allogeneic use in a first-degree or second-decree blood relative, or reproductive use.
Needless to say, the FDA spends another paragraph or so telling Genetech that they are selling drugs and biological products without the appropriate regulatory processes or steps being taken. This is a serious no-no. But then the FDA launches into the other part of the Warning Letter, by listing all of the extensive and very ugly observations the auditors put in their Form FDA 483.
I have seen FDA Warning Letters in which the FDA determined that a company was making a biological drug, and as a consequence was audited on the basis of needing to meet current Good Manufacturing Practices for drugs. However, in Genetech’s case, the FDA led off the list of sins with violations of the manufacturing requirements for facilities dealing in donor-derived materials.
Let’s start with the first point the FDA made in their Warning Letter about Genetech’s serious mistakes:
1. Failure of a responsible person to determine and document the eligibility of a cell or tissue donor based upon the results of donor screening and donor testing [21 CFR 1271.50(a)]. For example:
a. Genetech is the establishment responsible for making the donor eligibility determination, but since operations began in mid-2017, Genetech has failed to document whether donors of umbilical cord blood are eligible. Neither you, Liveyon, nor your suppliers have determined donor eligibility for the umbilical cord blood used to manufacture your products.
b. When Genetech receives relevant medical records, including the medical/social history interview and physical exams from its supplier, those records are not reviewed to determine donor eligibility.
The primary responsibility of a company dealing in donor-derived materials is to ensure the integrity of the donors, as a part of producing a safe product. The fact that Genetech failed at this vital obligation, and whose failure was discovered due to patients developing acute infections following treatment, doesn’t bode well for those acutely infected patients and others who might have been exposed to a variety of infectious agents, like HIV and Hepatitis. Not determining the eligibility of donors means that Genetech had no idea of the various infectious diseases those donors might have had.
I will continue in the next post with the serious implications of the failure of Genetech to meet even minimal standards in working with donor-derived materials, and the role Liveyon played in this debacle.