Among its most recent regulatory policy notices, the U.S. Food and Drug Administration issued a final guidance document for the minimal manipulation and homologous use of human cell, tissues, and cellular and tissue-based products (HCT/Ps). For any government agency whose decision-making operations are understood to be based on scientific principles and soundlylogical reasoning, adhering to such practice, while addressing public matters steeped in social and political controversy, can be a challenging mission.
The quality of the new guidance from the FDA falls far short of this standard. Although not explicitly acknowledged in the final guidance content, the fingerprints of negative social and political attitudes against stem cell treatments provided by private clinics are all over the document. These shaping forces appear in the form of regulations that are arbitrarily asserted instead of being based in scientific knowledge, practice, and reason. In addition to resulting in regulation that will encourage non-compliance and litigation, the FDA’s approach to preventing private clinic stem cell treatments will limit progress in stem cell regenerative medicine in general.
A Shift in Approach to Stem Cell Treatments
The present situation could be remedied by a creative shift in the FDA’s approach to new stem cell treatments performed in the course of general medical practice. Instead of pursuing its current false dichotomy that HCT/Ps must be considered as either drugs requiring traditional FDA approval or non-drugs requiring no approval, the FDA should develop a new regulatory paradigm. A new approach is essential to evaluate the long-term safety and efficacy of new stem cell treatments as they are being practiced in the short-term.
Although the main motivation for the final guidance for minimal manipulation and homologous use of HCT/Ps is not disclosed in the document, it was stated quite clearly in the FDA Commissioner’s recent statement anticipating issuance of the guidance. This guidance is intended to serve as an immediate enforcement basis (with the FDA exercising discretion during the first 36 months) for preventing the manufacture and treatment applications of HCT/Ps without FDA authorization. The described regulatory policies will render a large proportion of current treatments in private stem cell clinics in violation, unless they expeditiously began to adhere to conventional FDA regulations for clinical trial authorization and drug or biologics approval. Though the final guidance language emphasizes the well-established FDA mission to insure patient safety and clinical effectiveness, it does not mention the implicit standards of adhering to scientific principles and sound reason.
A good rule of thumb for understanding seemingly arbitrary and inconsistent rationales in a document, whose contents is presented as being based on scientific principles and reason, is to recognize that an undisclosed motivating factor is in force. Many of these occurrences in the new guidance can be explained by the FDA walking a tightrope to preserve the use of certain HCT/Psfor accepted clinical treatments while outlawing the use of related HCT/Ps for treatments in private clinics. Cells extracted from adipose tissue are an excellent example of this balancing act with an underlying understated motivation. Such cell populations have been shown to contain tissue stem cells, which are in high demand for treatments in private clinics because of well-established procedures for their harvest and application.
Contesting the FDA’s Guidance on HCT/Ps
However, the minimal manipulation rule requires that treatments with such cell populations follow FDA regulations for drugs or biologics. To justify this requirement, the FDA asserts, arbitrarily, that adipose tissue’s structural and cushioning properties must be maintained to avoid conventional regulation of its therapeutic use. This stipulation allows the widespread use of autologous fat injections in cosmetic surgery to continue unhampered. The stipulation is also inconsistently applied from one tissue to the next as pre-existing motivations dictate.
So, the gross manipulation of the structural integrity of bone marrow, required for the isolation and use of bone marrow cells, is allowed within the same guidance. Of course, there are many bone marrow cell therapies that pre-exist in general medical practice. Furthermore, to justify this guidance, the FDA makes a purely conjectural argument that undisrupted tissues are necessarily safer and more effective for cell therapies. One day, there may be scientific knowledge that supports this assertion, but presently it is only a poorly veiled contrivance.
The homologous use rule is similarly arbitrary. Right away, the lawyerly language “objective intent” warns of arbitrary contrivances presented as scientific rationales. For example, intact amniotic membranes used to accelerate the healing ofinjured heterologous organs qualify as homologous usage.Yet, isolated amniotic stem cells do not qualify for injection into heterologous tissue sites. It is not surprising, then, that the use of the intact membranes for repair and protection of other organs is already an approved practice. Conversely, injection of amniotic membrane-derived cells in private clinics is not.
The Challenge of Overseeing the Stem Cell Medical Field
The guidance that the FDA produced to justify its planned hobbling of private stem cell clinics is fundamentally antithetical to the scientific principles of the very studies that it now regulates. No drug studies or biologics studies are based on the nature of the evaluated agent in its pre-treatment state. To the contrary, the measure of safety and effectiveness is only in terms of the agent’s interaction with the patient. So, preservation of the donor state and donor function of HCT/Ps cannot, a priori, be a valid scientific basis for requiring FDA regulation. There are likely to be many scenarios in which disruption of the donor HCT/P’s state and function will, in fact, still contribute to safe and effective cell therapy treatments.
Fortunately, FDA guidances can be updated and revised. It may be that the history and mission of the FDA make it poorly suited to take on the challenge of overseeing the now very active stem cell medical field. However, with some creative vision, the FDA could advance within its existing charge and jurisdiction to manage this current remarkable moment of medical practice research to greater advantage for present and future patients.
The beginning of such a change in approach is developing sound knowledge of the nature and quality distribution of stem cell treatments in the many hundreds of private U.S. clinics. There are too many poorly informed aspersions cast by a few against the important efforts of the many private stem cell clinics as a group. Organizing and harnessing this vast and varied knowledge on how HCT/Ps may impact human health can allow the FDA to regain control of its stated mission of insuring safety and effectiveness.
About the Author: James L. Sherley, M.D., Ph.D. is the founder and director of stem cell biotechnology company Asymmetrex. Asymmetrex markets the only technology available for specific counting of therapeutic adult tissue stem cells to certify their dose and quality.