The U.S. Food and Drug Administration (FDA) on Thursday (Dec 20) said it had sent a letter to San Diego-based Genetech, Inc, warning the company for marketing non-FDA-approved stem cell products and for non-compliance with “current good tissue practice (CGTP) and current good manufacturing practice (CGMP) requirements.”
The agency has also issued warning letters to other manufacturers and healthcare providers involved in non-FDA-approved stem cell treatments.
The rebuke came in the wake of recent cases of serious infections following unapproved stem cell therapies.
At least a dozen patients in three states fell critically ill after receiving non-FDA-approved stem cell injections derived from umbilical cord blood, said the U.S. Centers for Disease Control and Prevention (CDC) in a report published Thursday (Dec 20).
A CDC investigation team led by Kiran Perkins discovered that seven patients in Texas, four in Florida, and one in Arizona were seriously infected after receiving Genetech-processed and Liveyon-distributed stem cell injections or infusions.
The infections, ranging from bloodstream and joint infections to epidural abscesses, among others, were so serious that all twelve patients had to be hospitalized; thankfully, no deaths were reported.
FDA approval for stem cell use is subject to meeting two main criteria: one, all stem cell products have to be derivatives of umbilical cord blood, and two, they can only be used in hematopoietic and immunologic reconstitution.
The CDC findings reveal that as many as eleven of the twelve infected patients were treated for pain or orthopedic conditions, which are non-hematopoietic in nature and, therefore, constitute a breach of FDA guidelines.
“[The] investigation highlights the serious potential risks to patients of stem cell therapies administered for unapproved and unproven uses other than hematopoietic or immunologic reconstitution,” says the report.
It goes on to point out that “many companies, clinics, and clinicians continue to market products from various sources as treatment for orthopedic, neurologic, and rheumatologic conditions without FDA approval.”
“The letters we’re issuing today to manufacturers, health care providers and clinics around the country are a reminder that there’s a clear line between appropriate development of these products and practices that sidestep important regulatory controls needed to protect patients,” said FDA Commissioner Scott Gottlieb in a press release.
Gottlieb assured that not only was the FDA committed to introducing new policies to ensure safe manufacturing practices for stem cell-based medicines, it was also mobilizing additional resources for the proper enforcement of these policies.
“We remain committed to supporting the development of safe and effective cell-based regenerative medicine and advancing our comprehensive regenerative medicine policy framework,” said the FDA commissioner.
“These efforts include our work to encourage manufacturers to engage with the FDA early so that we can provide guidance about any applicable regulatory requirements,” Gottlieb added.
While the agency is steadfast about taking action against non-compliers, it also wants to ensure that patients are not deprived of access to “safe and effective regenerative medicine products as efficiently as possible,” said Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research.
Companies that fail to mend their ways are likely to face “enforcement action such as seizure, injunction or prosecution,” warns FDA.
Perkins and his team ran tests on sealed vials at the Texas and Florida clinics where the patients received treatment and arrived at the conclusion that the bacterial contamination of the products occurred before distribution, effectively putting the responsibility on questionable manufacturing practices.
“Umbilical cord blood cannot be decontaminated after collection because there are currently no validated processes for sterilization, so manufacture of derived products must be highly controlled to prevent distribution of contaminated products,” the researchers wrote in their report.
The fact that both Genetech and Liveyon are registered with FDA does not mean they have the agency’s approval for, respectively, processing and distributing these products.
“The Genetech-processed, Liveyon-distributed product is not FDA-approved or lawfully marketed,” says the CDC report.
“Though Genetech and Liveyon are registered with FDA, such registration is not a form of FDA approval,” it said, adding that “FDA registration alone does not demonstrate compliance of firms or their products with the law.”
The CDC appealed to healthcare givers and receivers to report “any adverse events related to treatment with the Genetech/Liveyon products or any unapproved stem cell therapies to FDA’s MedWatch Safety Information and Adverse Event Reporting Program.”
In the letter to Genetech, FDA’s Program Division Director for the Office of Biological Products Operations, Karlton Watson, listed several significant CGTP and CGMP deviations, in addition to the earlier deviations the agency had already informed the company about.
“FDA has found additional significant deviations upon further review of the information collected during the June 2018 inspection,” read the letter addressed to Genetech president Edwin N. Pinos.
“The deficiencies include, but are not limited to, the following,” Watson wrote, going on to list 19 instances of non-compliance, in detail.