Dr. Centeno’s abstract was accepted for a presentation in front of the Tissue Engineering and Regenerative Medicine Society in Orlando In December. The Topic will be a scientific risk analysis of FDA Regulation of Autologous Stem Cells.
Submitted Abstract is below:
Should Autologous Stem Cells be Regulated the same as Mass produced Drugs?
Christopher J. Centeno, M.D.
Adult autologous stem cells (A-ASC’s) show great promise in research and early pre-clinical/clinical use. These cells have the potential to revolutionize medicine by differentiating into repair tissues or exerting paracrine effects to assist in tissue healing. In 2005, the FDA dramatically, and quietly, changed its regulatory approach with potential to upset the “great wall” between medical practice and mass drug production. In this year, the agency made changes to the 361 Public Health Service act to classify certain A-ASC’s (based on more than minimal processing) as a biologic drugs requiring pre-market, federal approval before use for sale in interstate commerce. Before 2005, this drug production status could have only applied to allogeneic tissues (i.e. cells that were mass produced in a vials for mass distribution). After 2005, this was applied to all human tissue. Since that time the agency has clarified that it considers “more than minimally manipulated” autologous tissue and cells to be biologic drugs. The agency now applies this same rule equally to autologous stem cell processing centers participating in interstate commerce as well as medical practices using autologous stem cells as part of one medical practice.
The agency has traditionally gone to great lengths to differentiate one on one medical care risks (over which it has no authority) from one on many drug and device production risks (it’s congressional mandate). However, after this subtle change in its regulations, the agency drew a regulatory, public health risk line through a one on one autologous tissue risk for the first time. For example, instead of only claiming authority over mass produced donor cells in a vial, the agency asserted authority over the re-implantation of the patient’s own tissue.
This wall between the agency and the practice of medicine has been defined by many court cases, but the case the agency brought against an Alabama physician (United States v. Evers) is illustrative. In this case, Dr. Evers was prosecuted by the government for using prescription drugs off label. The judge sided with Dr. Evers and explained why the FDA should not interfere with the practice of medicine. For example, the Court noted that a drug’s package insert is not the most up-to-date information on the drug’s uses. New uses are often discovered, reported through medical journals or seminars, and may become widely used in the medical profession; however, the drug manufacturer may not have sufficient financial or other interests to pursue FDA approval for the new uses. Further, if a doctor must prescribe and treat only within “federally sanctioned” methods, this would result in medical stagnation at the best, as physicians await drug manufacturers’ initiative and FDA approval. The court reasoned, “A free, progressive society has an enormous stake in recognizing and protecting this right of the physician.”
The best everyday example of the line FDA has drawn between one on one medical care risks and one on many public health risks, is how it currently handles compounded pharmaceuticals. In the Compliance Policy Guideline for compounding pharmacies, the agency states that since it doesn’t regulate the practice of medicine or pharmacy, that it will only attempt to interfere in this relationship if a pharmacy is compounding drugs in advance of receiving a prescription, manufacturing on a commercial scale, or compounding drugs for resellers or for wholesale use. In essence, the FDA will only intervene if the pharmacy crosses the line and departs from filing a single patient’s prescription and starts mass manufacturing of lots of drugs. However, the agency has not shown the same digression in its regulatory framework for autologous cell therapy and this marks a stark change in agency policy toward physicians. Since A-ASC’s used as part of a physician’s practice can only represent a one on one medical care risk because they are derived from the same patient in which they will be re-implanted, FDA, has now drawn the risk line through this one on one medical care risk and assigned it a mass production, public health risk status. This is despite rrecent publication on autologous stem cell treatment risks shows these risks to be substantially less than traditional one on one surgical care.
In summary, the assertion by FDA that certain processing steps for autologous stem cells turns those cells into a one on many drug production risk is not supported by an additional public health impact beyond any other one on one medical care risk. Furthermore, the agency’s decision to insert itself into the practice of medicine by drawing a line through one procedure, sets an interesting precedent. Where does this line get moved to in the future? Do certain compounded drugs get assigned a drug manufacture risk? Certain fertility procedures? Certain high risk surgeries? Certain high risk surgeries involving cells?
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4. USFDA, Pharmacy Compounding-Compliance Policy Guideline 460.200. Federal Register, Jun 7 2002. 67.
5. Centeno, C.J., et al., Safety and complications reporting on the re-implantation of culture-expanded mesenchymal stem cells using autologous platelet lysate technique. Curr Stem Cell Res Ther, 2010. 5(1): p. 81-93.