Authored by: Mo Heidaran, Mark Levi and Robert Iser
In 2016, Knoepfler and Turner published a detailed assessment of an industry which is based on direct marketing of stem cell products to patients which was observed to be growing throughout US at an alarming rate (https://www.cell.com/action/showPdf?pii=S1934-5909%2816%2930157-6). According to a public database (https://ipscell.com/stem-cell-clinic-list-database/) there are close to 350 stem cell clinics in US selling unapproved stem cell treatments to the public using internet-based marketing and promotional claims for almost 30 different indications. These stem cell clinics claim that collecting cells from a patient and performing a few minor manufacturing/processing steps before administration back to the same patient should not pose any risk to the patient and therefore, should not be regulated by FDA. The claim of “practice of medicine” is an argument that these products meet the regulatory definition of Human Cells, Tissues, and Cellular and Tissue-Based Products (HCT/Ps) not requiring premarket approval according to §361 of Public Health Service Act (Minimally manipulated and used for homologous indications and are considered autologous).
FDA has expressed concern about the current trend of direct to consumer marketing of these unapproved biological drugs. For this reason, the agency has issued several guidance documents to further clarify the regulatory framework for products that are manufactured by these stem cell clinics. An overview of the framework is outlined in a suite of guidance documents available on the FDA website (https://www.fda.gov/BiologicsBloodVaccines/CellularGeneTherapyProducts/ucm585218.htm).
FDA is clearly concerned that these types of stem cell products could be manufactured under non-cGMP conditions which do not meet the minimum regulatory standards for product quality. As a result, these products have potential to affect the health of patient by causing acute or chronic microbial infections, potentially leading to worsening of the patient’s condition or other serious adverse events. These concerns are no longer hypothetical as the agency has received numerous reports of patients falling ill after using these unapproved products or becoming adversely impacted by the treatment (https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm628918.htm).
A recent letter by Director of CBER’s Office of Compliance and Product Quality (OCBQ) to Genetech highlights this point (https://www.fda.gov/downloads/BiologicsBloodVaccines/CellularGeneTherapyProducts/UCM628912.pdf)
“FDA’s final guidance, Regulatory Considerations for Human Cells, Tissues, and Cellular and Tissue-Based Products: Minimal Manipulation and Homologous Use, issued in November 2017, informed manufacturers, health care providers, and other interested parties about the Agency’s compliance and enforcement policy for these products. The guidance outlined FDA’s intent to exercise enforcement discretion for the first 36 months following issuance of the guidance for certain products with respect to FDA’s IND and premarket approval requirements when the use of the product does not raise reported safety concerns or potential significant safety concerns. This period provides manufacturers time to comply with the IND and premarket approval requirements and engage with FDA to determine whether they need to submit an IND or marketing authorization application, and if so, to submit their application to FDA”.
This statement should be taken seriously by stem cell clinics that are engaged in marketing of unapproved drugs in the US. The companies that engage in marketing and selling of these unapproved drugs have until November of 2020 to become fully compliant.