Stem cell clinics facing rough weather
Stem cell therapies may offer the potential to treat diseases or conditions for which few treatments exist. Sometimes called the body’s “master cells,” stem cells are the cells that develop into blood, brain, bones, and all of the body’s organs. They have
The U.S. Food and Drug Administration (US FDA), in two complaints filed on May 9, in federal court, is seeking permanent injunctions to stop two stem cell clinics from marketing stem cell products without its approval and for significant deviations from current good manufacturing practice requirements.
“Cell-based regenerative medicine holds significant medical opportunity, but we’ve also seen some bad actors leverage the scientific promise of this field to peddle unapproved treatments that put patients’ health at risk. In some instances, patients have suffered serious and permanent harm after receiving these unapproved products. In the two cases filed on May 9, the clinics and their leadership have continued to disregard the law and more importantly, patient safety. We cannot allow unproven products that exploit the hope of patients and their loved ones,” said FDA Commissioner Scott Gottlieb, M.D. “We support sound, scientific research and regulation of cell-based regenerative medicine, and the FDA has advanced a comprehensive policy
framework to promote the approval of regenerative medicine products. But at the same time, the FDA will continue to take enforcement actions against clinics that abuse the trust of patients and endanger their health with inadequate manufacturing conditions or by purporting to have treatments that are being manufactured and used in ways that make them drugs under the existing law but have not been proven safe or effective for any use.”
A permanent injunction is being sought against US Stem Cell Clinic LLC of Sunrise, Florida, its Chief Scientific Officer Kristin Comella and its co-owner and managing officer Theodore Gradel for marketing to patients stem cell products without FDA approval and while violating current good manufacturing practice requirements, including some that could impact the sterility of their products, putting patients at risk. The FDA is taking this action because US Stem Cell Clinic did not address the violations outlined in a warning letter to the clinic and failed to come into compliance with the law. The FDA is seeking an order of permanent injunction requiring US Stem Cell and the individual defendants to cease marketing their stem cell products until, among other things, they obtain necessary FDA approvals and correct their violations of current good manufacturing practice requirements.
The FDA is also seeking a permanent injunction to stop California Stem Cell Treatment Center Inc., with locations in Rancho Mirage and Beverly Hills, California; Cell Surgical Network Corporation of Rancho Mirage, California; and Elliot B. Lander, M.D. and Mark Berman, M.D., from marketing to patients stem cell products without FDA approval. Berman and Lander control the operations of approximately 100 for-profit affiliate clinics, including the California Stem Cell Treatment Center. The FDA is seeking an order of permanent injunction requiring California Stem Cell Treatment Center Inc. and Cell Surgical Network Corporation and the individual defendants to cease marketing their stem cell products until, among other things, they obtain necessary FDA approvals and correct their violations of current good manufacturing practice requirements.
US Stem Cell Clinic
The FDA issued a warning letter to US Stem Cell Clinic in August 2017 for marketing stem cell products without FDA approval and for significant deviations from current good manufacturing practice requirements, including some that could impact the sterility of their products. The warning letter also cited an FDA inspection of the clinic which found that it was processing adipose tissue (body fat) into stromal vascular fraction (a cellular product derived from body fat) and administering the product both intravenously or directly into the spinal cord of patients to treat a variety of serious diseases or conditions, including Parkinson’s disease, amyotrophic lateral sclerosis (ALS), chronic obstructive pulmonary disease (COPD), heart disease and pulmonary fibrosis. The FDA has not approved any biological products manufactured by US Stem Cell Clinic for any use.
During the inspection of US Stem Cell Clinic in April and May 2017, FDA investigators also documented evidence of significant deviations from current good manufacturing practices in the manufacture of at least 256 lots of stem cell products by the clinic. For example, the clinic was cited for its failure to establish and follow appropriate written procedures designed to prevent microbiological contamination of products purporting to be sterile, which puts patients at risk for infections.
The complaint for permanent injunction against US Stem Cell Clinic was filed by the U.S. Department of Justice on behalf of the FDA in the US. District Court for the Southern District of Florida.
California Stem Cell Treatment Center and Cell Surgical Network Corporation
In August 2017, the FDA took action to prevent the use of a potentially dangerous and unproven treatment belonging to StemImmune Inc. in San Diego, California and administered to patients at the California Stem Cell Treatment Centers in Rancho Mirage and Beverly Hills. On behalf of the FDA, the U.S. Marshals Service seized five vials of Vaccinia Virus Vaccine (Live) – a vaccine that is reserved only for people at high risk for smallpox, such as some members of the U.S. military. The seizure came after FDA inspections at StemImmune and the California Stem Cell Treatment Centers confirmed that the vaccine was used to create an unapproved stem cell product (a combination of excess amounts of vaccine and stromal vascular fraction – a cellular product derived from body fat). The product was then administered to cancer patients with potentially compromised immune systems and for whom the vaccine posed a potential for harm, including the possibility of inflammation and swelling of the heart and surrounding tissues. The unproven and potentially dangerous treatment was being injected intravenously and directly into patients’ tumors.
California Stem Cell Treatment Center products are also being used for the experimental treatment of patients who suffer from a variety of serious diseases or conditions, including cancer, arthritis, stroke, amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), macular degeneration, Parkinson’s disease, chronic obstructive pulmonary disease (COPD) and diabetes. The FDA has not approved any biological products manufactured by California Stem Cell Treatment Center for any use.
During inspections of California Stem Cell Treatment Center’s Beverly Hills and Rancho Mirage facilities in July 2017, FDA investigators documented, among other violations, evidence of significant deviations from current good manufacturing practice requirements. For example, the clinics were cited for failing to establish and follow appropriate written procedures designed to prevent microbiological contamination of products purporting to be sterile, which puts patients at risk for infections.
The complaint for permanent injunction was filed
by the U.S. Department of Justice on behalf of the FDA in the U.S. District Court for the Central District of California.
These cases support the FDA’s comprehensive policy framework for the development and oversight of regenerative medicine products, including novel cellular therapies. The FDA issued four guidance documents in November 2017, two final and two draft that build upon the FDA’s existing risk-based regulatory approach. Under this framework the FDA detailed its efficient, science-based process for helping to ensure the safety and effectiveness of these therapies, while supporting development in this area. One of the two draft guidance documents laid out a novel and efficient clinical development model by which promising cell-based products could pursue review and approval by the FDA. The suite of guidance documents also describes a risk-based framework for how the FDA intends to focus its enforcement actions against those products that raise reported safety concerns or potential significant safety concerns.
ISSCR applauds Federal injunctions
Pleased with federal injunctions against the stem cell clinics, the International Society for Stem Cell Research (ISSCR), with more than 4,000 members from over 60 countries, states that federal prosecutors in the U.S. have taken action to halt the marketing and delivery of unproven stem cell treatments at clinics they allege are operating outside of FDA regulation.
ISSCR in a release notes that according to court filings announced by the Department of Justice and the FDA, these clinics have been offering stem cell interventions whose safety and effectiveness have not been established in clinical trials, nor have they gone through the FDA approval process. If true, these clinics put patients at unknown risk, and elude regulatory authority. A number of Americans have already been blinded or paralyzed from unproven stem cell treatments, some of which were marketed in a way that caused patients to believe they were participating in legitimate clinical trials.
“Holding clinics responsible for violating regulations will put others on notice that they can no longer operate outside the Comprehensive Regenerative Medicine Policy Framework set forth by the FDA last year,” says ISSCR president Hans Clevers. “We’re pleased that the FDA is enforcing these guidelines, and hope this legal action will send a firm message to the many rogue clinics pedaling unproven stem cell interventions that they are not above the law,” he said.
The ISSCR has long been concerned with the proliferation of clinics offering stem cell interventions
that have little basis in science or medicine and that prey upon the hopes of desperate patients. The organization offers its assistance and scientific expertise to governments and regulatory authorities worldwide as they try to curtail this problem.
ISCT proposes wider action
Reacting to the US FDA action on seeking court orders preventing two US stem cell clinics administering unproven cellular therapy treatments to patients, Vancouver based International Society Cell and Gene Therapy (ISCT), the global professional society of clinicians, researchers, regulatory specialists, technologists and industry partners in the cell and gene therapy sector, says “The most recent FDA actions highlight to the entire cell therapy community that the Unproven Cellular Therapies (UCT), business stretches across the globe, not just in specific regions where regulations are less tight.”
Dr. Massimo Dominici, chair of the ISCT Presidential Task Force (PTF) on the Use of Unproven Cellular Therapies and professor of oncology at the University of Modena and Reggio Emilia, Italy says, “It is vital that regulators, as recently demonstrated by the FDA, continue to identify and shut down clinics conducting unproven and potentially harmful cellular interventions. However, all representatives of the ISCT Presidential Task Force agree that the job cannot be left to regulators only. There is no magic bullet for UCT with complex challenges. Patients affected by diseases with a high-unmet medical need have few options. It is up to the cell therapy community to collectively drive more therapies through approval, reduce costs through innovative development and manufacturing strategies and educate the public and patients about the dangers of unproven cellular therapy. As a result, ISCT will continue to coordinate global interdisciplinary efforts to implement these longer-term solutions.”
ISCT noted that it has for a number of years been bringing groups together spanning the international cell and gene therapy community, including collaborations with more than 30 scientific societies and institutions, to lead and coordinate direct action to combat and raise awareness about unethical and unproven cellular therapies. It first discussed unproven cell therapies with the FDA in 2012. Direct action has ranged from establishing a multilateral task force, implementing a long term program of regulatory harmonization, to publishing a reference guide, translated in six languages, authored by 23 leading figures in the field, for the patient community.
“Cell and gene therapies are addressing a variety of currently unmet medical needs. Several products have been approved after demonstration of safety and clinical efficacy. Many more are currently progressing through clinical development. However, clinics offering potentially dangerous unproven cell therapies present a significant risk of eroding public confidence in our new, emerging field,” says John Rasko, President, ISCT and Head, Cell & Molecular Therapies, RPA Hospital, Sydney, Australia. “The FDA action, and wider collaborations at the ISCT Annual Meeting in May, have reinforced the need for ISCT and its members numbering over 1,500 across 50 countries to continue on its mission of promoting the development of, and access to, properly manufactured and documented cell and gene therapies to patients. As these approved therapies are delivered, this will ultimately reduce the demand for unproven treatments.”
According to a report authored by Paul Knoepfler, Institute of Pediatric Regenerative Medicine, Shriners Hospital for Children Northern California, Sacramento, and Leigh Turner and Center for Bioethics, School of Public Health, & College of Pharmacy, University of Minnesota and published on Jan 12, 2018 hundreds of businesses in the US currently advertise a wide range of non-US FDA-approved stem cell interventions. Between 2009 and 2014, the number of new US stem cell businesses with websites grew rapidly, at least doubling on average every year. From 2014 to 2016, approximately 90-100 new stem cell business websites appeared per year. More than 700 stem cell marketers were operating in the US.
In contrast, from 2012 to the present, regulatory activity in the form of FDA warning letters has been limited. These data point to a problematic disconnect between a rapidly expanding US direct-to-consumer stem cell industry and limited FDA oversight of this marketplace. More consistent, timely and effective FDA actions are urgently needed.