The creation of red blood cells for the blood transfusion markets highly represents an innovative approach of regenerative medicine with a medium term (5–10 year) prospect for first clinical study. This article describes a research analysis of a project to derive red blood cells from human embryonic stem cells, including the systemic challenges arising from (i) the selection of appropriate and viable regulatory protocols and (ii) technological constraints related to stem cell manufacture and scale up to clinical studies adapting Good Manufacturing Practice (GMP) standard. The method used for research analysis (Analysis of Life Science Innovation Systems (ALSIS)) deals with an innovative, demonstrates a new approach to social and natural science collaboration to foresight product development pathways. Issues arising along the development pathway include cell manufacture and scale-up challenges, affected by regulatory demands emerging from the innovation ecosystem (preclinical testing and clinical trials). Our discussion reflects on the efforts being made by regulators to adapt the current pharmaceuticals-based regulatory model to an allogeneic regenerative medicine product and the broader lessons from this case study for successful innovation and translation of regenerative medicine therapies, including the role of methodological and regulatory innovation in future development in the field.
The method applied for this project, Analysis of Life Science Innovation Systems (ALSIS)  uses a strategic mapping approach to project future business models and product development pathways (defined as the full range of activities required to bring a product from conception to end use, including design, production, marketing, distribution and support to the final consumer). These factors, broadly discussed under the control of the innovator, are embedded within an innovation ecosystem that includes the economic, regulatory, societal and political contexts that are beyond the control of the innovator, with either positive or negative impacts on the product development business plan. For the Blood pharma project, critical decision points within the product development pathway arose from the scientific and technological challenges of differentiating sufficient quantities of RBCs from stem cells meeting clinical grade GMP standards for different stages of pre-clinical and clinical testing; and the implications for product development and regulatory science of targeting the niche Thalassaemia market. The main innovation ecosystem components discussed in this paper are the regulatory system and the challenge of meeting requirements related to the use of conventional preclinical animal models and to the conduct of human clinical trials.
The sequence of decisions related to the scientific and technical challenges in developing the cultured product, showing the critical points in the overall pathway at which manufacturing and scale-up decisions would need to be finalised and where such decisions would interact with the regulatory system. The first concepts at the start of the critical path, obtaining a starting cell line and developing a working cell bank bring up the question of the expected starting material. In Between 2010-12 the project was using human embryonic stem cell (hESC) lines as the starting material, but the long-term plan was to use induced pluripotent stem cell (iPSC) lines. Factors favouring that choice included: the requirement for open-source hESC banking in the UK.
We found two vital observations from this research: (i) related to the innovative capacity of regenerative medicine therapies; and (ii) related to the potential role of interdisciplinary social science methods in supporting innovation processes.
Citation: J. Mittra , J. Tait , M. Mastroeni , M.L. Turner , J.C. Mountford and K. Bruce Identifying Viable Regulatory and Innovation Pathways for Regenerative Medicine doi:10.1016/j.nbt.2014.07.008
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Received: August 2014 Accepted: January 2015 Published: January 2015
The authors declare that they have no competing interests.
Funding: Open Access funded by Economic and Social Research Council.