Report of the international conference on regulatory endeavors towards the sound development of human cell therapy products.

The regulation of human cell therapy products is a key factor in their development and use to treat human diseases. In that regard, there is a recognized need for a global effort to develop a set of common principles that may serve to facilitate a convergence of regulatory approaches to ensure the smooth and efficient evaluation of products. This conference, with experts from regulatory agencies, industry, and academia, contributed to the process of developing such a document. Elements that could form a minimum consensus package of requirements for evaluating human cell therapy products were the overall focus of the conference. The important regulatory considerations that are unique to human cell therapy products were highlighted. Sessions addressed specific points that are different from those of traditional biological/biotechnological protein products. Panel discussions complemented the presentations. The conference concluded that most of the current regulatory framework is appropriate for cell therapy, but there are some areas where the application of the requirements for traditional biologicals is inappropriate. In addition, it was agreed that there is a need for international consensus on core regulatory elements, and that one of the major international organizations should take the lead in formulating such a consensus document.

Do human leukocyte antigen-typed cellular therapeutics based on induced pluripotent stem cells make commercial sense?

The promise of off-the-shelf cellular therapeutics (CTPs) based on allogeneic induced pluripotent stem cells (iPSCs) may be hindered by alloimmunity, leading many to suggest that such products could be based on a series of human leukocyte antigen (HLA)-typed iPSC lines allowing at least some degree of tissue matching. While based on sound scientific principles, this suggestion presupposes that other immune responses will not be limiting. Technically this approach would present a number of major challenges, the first being the development of a suitably reliable reprogramming method amenable to validation that results in highly consistent iPSC lines. Further, the resulting array of HLA-typed iPSCs would need to be shown to be capable of being manufactured into the same CTP and exhibit comparable quality, safety, and efficacy. When the enormities of these challenges are laid out, it becomes apparent that the manufacturing and product development challenges would be unprecedented. Given the uncertainties and lack of clinical experience with iPSC-based CTPs at this time, the financial costs and commercial risks do not appear to be acceptable.