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The agency sent a warning letter to Roche’s Genetech for marketing unapproved stem cell products and puts other stem cell firms and providers on notice.
Editor’s note: An earlier posting of this article incorrectly identified Genetech, Inc. as a subsidiary of Roche. The companies are not affiliated. We apologize for the error.
On Dec. 20, 2018, FDA announced that it sent a warning letter to Genetech, a San Diego, CA-based biotechnology company, about umbilical cord blood-derived cellular products distributed by Liveyon, a distributer of umbilical cord-derived products to physicians for use in regenerative medicine therapies. FDA is also sending letters to other firms and providers offering stem cell treatments notifying them of agency's regenerative medicine policy framework.
The letter addresses Genetech and its president, Edwin N. Pinos, for marketing stem cell products without FDA approval and for significant deviations from current good tissue practice (CGTP) and current good manufacturing practice (CGMP) requirements, including some violations that may have led to microbial contamination, potentially causing serious blood infections in patients. Genetech processed umbilical cord blood into unapproved human cellular products, which was distributed by Liveyon.
FDA inspected Genetech's facility in June 2018 and found the company was processing cellular products from human umbilical cord blood for administration by intra-articular (joint) injection, intravenous injection, or application directly to the affected tissue to treat a variety of orthopedic conditions. These products were distributed by Liveyon in Yorba Linda, CA as ReGen5, ReGen10 and ReGen30. The Genetech products are not intended for homologous use (products that are intended for the same function in the recipient as the donor), and while the products have a systemic effect, they are not intended for allogeneic (genetically similar) use in a first or second-degree blood relative. As such, the products are regulated as both drug and biological products. To lawfully market these products, an approved biologics license application is needed. While in the development stage, the products may be used in humans only if an investigational new drug application is in effect. However, no such licenses or investigational new drug applications exist for the Genetech-processed, Liveyon-distributed products.
During the inspection, the agency documented evidence of significant deviations from CGTP and CGMP requirements in the manufacture of the umbilical cord blood-derived products, including deficient donor eligibility practices, unvalidated manufacturing processes, uncontrolled environment, lack of control over the components used in production, and a lack of defined areas or a control system to prevent contamination and mix-ups. FDA reports that these deviations pose a significant risk that the products may be contaminated with microorganisms or have other serious product quality defects.
FDA and the Centers for Disease Control and Prevention have received numerous reports of safety issues, including those involving microbial contamination and are aware of 12 patients who received Genetech products from Liveyon and subsequently became ill due to blood and other infections caused by a number of bacteria, including Escherichia coli (E. coli), as described in a forthcoming Morbidity and Mortality Weekly Report (MMWR), titled "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."
In September 2018, Liveyon suspended shipment of all product pending an inquiry by FDA into the source of the adverse reactions. Liveyon also voluntarily recalled all Genetech products it may have distributed.
FDA requested a response from Genetech, within 15 working days of the letter's issuance, that details how the deviations noted in the warning letter will be corrected. Deviations not corrected by companies and owners could lead to enforcement action such as seizure, injunction, or prosecution.
Additionally, as part of FDA's overall goal to support the responsible development of safe and effective products for patients, the agency is sending letters to reiterate FDA's compliance and enforcement policy to other manufacturers and health care providers who may be offering stem cell treatments.
"We remain committed to supporting the development of safe and effective cell-based regenerative medicine and advancing our comprehensive regenerative medicine policy framework,” said FDA Commissioner Scott Gottlieb, MD, in an agency press release. “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. Even though a few sponsors have come to us, we are discouraged by the overall lack of manufacturers wanting to interact with the agency in this enforcement discretion period. 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. Time is running out for firms to come into compliance during our period of enforcement discretion. We'll be increasing our oversight related to cell-based regenerative medicine as part of our comprehensive plan to promote beneficial innovation while protecting patients."
Health care professionals and consumers should report any adverse events related to treatments with the Liveyon products, Genetech products, or other stem cell treatments.