FDA Sends Warning to Companies for Offering Unapproved Umbilical Cord Blood Products

The U.S. Food and Drug Administration (FDA) has warned Liveyon Labs Inc. (Liveyon Labs) and Liveyon LLC, of Yorba Linda, California, and their presidents and chief executive officers, Roya Panah and John W. Kosolcharoen, for processing and distributing unapproved products derived from umbilical cord blood. They have also been warned regarding significant deviations from current good tissue practice (CGTP) and current good manufacturing practice (CGMP) requirements, including deficient donor eligibility practices, inadequate aseptic practices to prevent contamination and deficient environmental monitoring. These deviations create potential significant safety concerns that put patients at risk. The companies’ unapproved products derived from umbilical cord blood are PURE and PURE PRO.

In addition to the warning letter issued to Liveyon Labs and Liveyon LLC earlier this month, the FDA sent untitled letters to RichSource Stem Cells, Inc., and Chara Biologics, Inc., for offering unapproved stem cell products to patients. The agency also recently sent 20 letters to manufacturers and health care providers noting that it has come to our attention that they may be offering unapproved stem cell products, reiterating the FDA’s compliance and enforcement policy.

"The FDA’s mission includes protecting public health by helping to ensure the safety and efficacy of medical products that patients rely on. The agency is aware that there are establishments who prey upon vulnerable populations by commercially marketing stem cell products with false and misleading claims about their effectiveness for treating serious diseases," said Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research. "The FDA is taking this action today because Liveyon Labs and Liveyon LLC failed to take appropriate measures to protect patient safety. As evidenced by the number of actions that the agency has taken this month alone, there are still many companies that have failed to come into compliance with the Federal Food, Drug, and Cosmetic Act and FDA’s regulations during the period in which the agency intends to exercise enforcement discretion for certain products with respect to FDA’s investigational new drug and premarket approval requirements, when the use of the product does not raise reported safety concerns or potential significant safety concerns. This period, which ends in November 2020, has allowed product manufacturers time to engage with the FDA to determine if they need to submit a marketing authorization application and, if so, seek guidance on how to submit their application to the FDA for approval. The agency continues to urge these manufacturers to engage with the agency about their regulatory requirements in the coming months."

An FDA inspection of the Liveyon Labs and Liveyon LLC facility in May revealed the companies were processing and distributing products derived from human umbilical cord blood for use in patients who were unrelated to the donors. Because these products are not intended for homologous use only (i.e., to perform the same basic function or functions in the recipient as in the donor) and fail to meet other criteria set forth in applicable FDA regulations, they are regulated as both drugs and biological products. Therefore, 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 (IND) is in effect. However, no such licenses or INDs exist for the PURE and PURE PRO products marketed by Liveyon Labs and Liveyon LLC.

During the inspection, the FDA documented evidence of significant deviations from CGTP and CGMP requirements in the manufacture of the PURE and PURE PRO products, including deficient donor eligibility practices, such as failing to screen donors’ relevant medical records for risk factors for communicable diseases; inadequate aseptic practices, such as failing to follow procedures to prevent microbiological contamination; and deficient environmental monitoring, such as failing to establish a system for cleaning and disinfecting the processing room and equipment. These deviations pose a significant risk that the products may be contaminated with viruses or other microorganisms or have other serious product quality defects, which could potentially lead to patient harm.

In addition to the warning letter released today, the FDA has issued a safety alert about exosome products. Certain clincs across the country, including some that also manufacture or market violative "stem cell" products, are now also offering exosome products to patients. FDA’s safety alert informs the public, especially patients, health care practitioners and clinics, of multiple recent reports of serious adverse events experienced by patients in Nebraska who were treated with unapproved products marketed as containing exosomes. These reports were brought to the FDA’s attention by the Centers for Disease Control and Prevention, among others, and the agencies worked with the Nebraska Department of Health and Human Services. The FDA is carefully assessing this situation along with our federal and state partners.

As highlighted in 2017 with the release of the FDA’s comprehensive regenerative medicine policy framework, including the FDA’s final guidance (Regulatory Considerations for Human Cell, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use), the FDA is applying a risk-based approach to compliance and enforcement of cell-based regenerative medicine products, taking into account how products are being administered as well as the diseases and conditions for which they are intended to be used. The agency noted that it intends to exercise enforcement discretion for certain products until November 2020 with respect to the FDA’s IND application and premarket approval requirements when the use of the product does not raise reported safety concerns or potential significant safety concerns. However, the FDA does not intend to exercise such enforcement discretion for those products that pose a reported safety concern or a potential significant safety concern to patients. As reflected by this warning letter and other correspondence issued by the agency, the FDA will continue to take appropriate steps to protect the public health.

The FDA continues to facilitate the development of safe and effective cellular therapies and offers opportunities for engagement between potential manufacturers and the agency, such as through the INTERACT program. The agency also encourages the use of its expedited programs whenever applicable, in addition to a collaborative developmentExternal Link Disclaimer of products with industry and the agency. In addition, the FDA recently announced a temporary program called the Tissue Reference Group (TRG) Rapid Inquiry Program (TRIP), which is intended to assist manufacturers of human cells, tissues and cellular and tissue-based products (including stem cells) to obtain a rapid, preliminary, informal, non-binding assessment from the agency regarding how their specific products are regulated.

The FDA requested a response from Liveyon Labs and Liveyon LLC 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 the companies and responsible individuals could lead to enforcement action such as seizure, injunction or prosecution.

Health care professionals and consumers should report any adverse events related to treatments with the PURE or PURE PRO products or other stem cell treatments to the FDA’s MedWatch Adverse Event Reporting program. To file a report, use the MedWatch Online Voluntary Reporting Form. The completed form can be submitted online or via fax to 1-800-FDA-0178. The FDA monitors these reports and takes appropriate action necessary to ensure the safety of medical products in the U.S. marketplace.

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