CBF

(also see mesenchymal stem cells, transfusion, autoimmune diseases, HIV positive patients, acute radiation injury, adverse events during bone marrow and PBSC donation)

 

iii. Regulatory Issues

  1. Will regulation be the death of cell therapy in the United States? Gastineau DA. Bone Marrow Transplant. 2004;33:777-80. Abstract

This thoughtful review is generally optimistic regarding a proposed answer to the question posed, and the author states that regulatory agencies are evolving into a cooperative, supportive position that will ultimately speed the introduction of safe and effective cell-based therapies to broad clinical use. Nevertheless, the author points out that voices of frustration are increasingly strident, suggesting that there is overregulation choking off progress in a promising area. There is also little question that the regulators are under intense political scrutiny, and the tolerance for any perceived error of regulation is small.

At least two means of approving cell therapy products can be contemplated. The first is the prevailing view held by the FDA. This current vision is that of the classic commercial model: a company seeks approval for a specific product which is then manufactured by the company for distribution or is licensed to specific manufacturer who then distributes the product. Manufacturing is defined as any substantial manipulation of cells beyond straight-forward collection and cryopreservation. The official designation is a tongue twisting "more than minimal manipulation." Manufacturing is not a word that rolls easily off the tongue of most investigators (although blood banks have become accustomed to it). The second is the blood bank model of blood product manufacturing, i.e, production of a range of products derived from whole blood.

The author states that we cannot ignore the political nature of regulation, and intolerance of risk for even apparently low-risk therapies. There exists a "zero risk" expectation in traditional blood bank products ("we spend millions and reduce the donor pool for theoretical risks"), which extends to cell therapy products. The author concludes with a statement that "regulators and the inventors must share the vision of safety, evolution and reasonable risk management to bring promising therapies to waiting patients." (emphasis added)

(Comment: Reasonable risk management is a concept that is not yet well developed at the FDA. There are significant differences between a unit of RBCs for transfusion and a cellular therapy product such as a unit of umbilical cord blood that has been harvested for transplantation. To discard a unit of RBCs merely to comply with an ineffective "zero risk" policy only wastes money and a product that can be replaced easily, but does not endanger patients. In contrast, to discard HLA-typed stem cells to satisfy a "zero risk" policy may destroy the optimal or only available product for a life saving transplant. Transplant physicians are skilled at balancing risks vs. benefits, and frequently allow for variances that would not be acceptable in transfusion medicine. Let us hope that the apparent conflict between a "zero-risk" policy and a policy of allowing reasonable risk management can be resolved.)