Regenerative medicine is used to describe a variety of procedures that involve using a patient’s own or other humans’ biologic material to prevent or treat disease. The current hot area is cell therapy, which often involves removing a patient’s cells, manipulating them in some manner and then replacing them in the patient. Cancer immunotherapy is probably the prototypical cell therapy. New medical techniques often bring regulatory uncertainty, and given the promise of these therapies, government agencies can help the process of getting into clinical use by clarifying regulatory requirements. The FDA has recently done that with cell and similar therapies, issuing or modifying four guidances. (FDA Guidances) Two of the guidances are finalized versions of earlier drafts. One specifies when removal of tissue or cells from an individual and replaced into that individual in the same surgical procedure would be exempt from regulation. The original purpose of the underlying regulation was to prevent transmission of communicable diseases. Since autologous translation in the same procedure poses minimal risk in this regard, the agency confirmed its exemption from regulation. But this exemption is very limited, given the need for a single procedure and that essentially no manipulation can be done to the tissue beyond cleaning, rinsing, sizing and shaping.
The second final guidance redefines the concepts of “minimal manipulation” and “homologous use” for purposes of exemption from premarket clearance. This would apply in situations which don’t meet the exemption in the first guidance, and other circumstances. It has significant importance, because therapies not exempt are subject to the full panoply of requirements for drug, device and/or biologics approval. Unfortunately or fortunately, depending on your perspective, most, indeed all, cell therapies likely won’t qualify for minimal manipulation, because that requires that the relevant biologic characteristics not be modified. Given that, the homologous use criteria is kind of irrelevant, but most cell therapies would meet that requirement, since they generally are intended to serve the same function. The new draft guidances relate more to regulatory processes. The first one addresses devices used in the performance of cell therapies and other regenerative medicine techniques. It basically says the devices may be considered with the underlying therapies to be a combination product, which somewhat simplifies the regulatory process for manufacturers. The second draft guidance relates to when a therapy may be eligible for expedited review under existing or new programs and what considerations should go into clinical trial designs for such therapies. Generally the therapy has to be for a serious condition for which existing therapies are inadequate.
While it is good that the FDA is providing guidance to developers of these new therapies, the really critical issue is how they can possibly be paid for. We have already seen how specialty drugs have nearly bent the system to a breaking point. Cell therapies have even higher price tags. While they are expensive to develop and operationalize, their promoters also seem to be expecting drug-like margins. That is the real problem. Payers and policymakers need to get out in front of this now.