Comparability & reimbursement for the translation of scalable, automated stem cell cultures

The research in this thesis focuses primarily on two critical challenges that inhibit the late stage translation of cell-based therapies and Regenerative Medicines (RMs). These include product comparability after a change in manufacturing process or site; and the reimbursement of RMs, in particular those which target multiple simultaneous indications, or Multimorbidity . The automation and standardisation of stem cell cultures also represent key themes of this thesis, which may facilitate the development of scalable, reproducible manufacturing processes for cell-based therapies. Furthermore, given the current uncertainty regarding the characterisation and potency of Human Mesenchymal Stromal (or Stem) Cells (hMSCs) that has inhibited the successful clinical translation of hMSC-based products, understanding the characterisation and putative modes of action of these cells was also a priority throughout this research. Also, due to the increasing number of Human Embryonic Stem Cell (hESC) derived therapies progressing towards market, and the industry-wide shift towards Human Induced Pluripotent Stem Cells (hiPSC) as an alternative to hESCs, the measurement of the growth and characterisation of these cells types represents an important method of demonstrating product comparability after alternative manufacturing process steps in the present thesis. Finally, due to the potential of hiPSCs as a source of large numbers of hMSCs, the culture conditions required to direct the differentiation of hiPSCs to hMSCs are explored

Comparability of automated human induced pluripotent stem cell culture: a pilot study

Consistent and robust manufacturing is essential for the translation of cell therapies, and the utilisation automation throughout the manufacturing process may allow for improvements in quality control, scalability, reproducibility and economics of the process. The aim of this study was to measure and establish the comparability between alternative process steps for the culture of hiPSCs. Consequently, the effects of manual centrifugation and automated non-centrifugation process steps, performed using TAP Biosystems’ CompacT SelecT automated cell culture platform, upon the culture of a human induced pluripotent stem cell (hiPSC) line (VAX001024c07) were compared. This study, has demonstrated that comparable morphologies and cell diameters were observed in hiPSCs cultured using either manual or automated process steps. However, non-centrifugation hiPSC populations exhibited greater cell yields, greater aggregate rates, increased pluripotency marker expression, and decreased differentiation marker expression compared to centrifugation hiPSCs. A trend for decreased variability in cell yield was also observed after the utilisation of the automated process step. This study also highlights the detrimental effect of the cryopreservation and thawing processes upon the growth and characteristics of hiPSC cultures, and demonstrates that automated hiPSC manufacturing protocols can be successfully transferred between independent laboratories

SciPy 1.0: fundamental algorithms for scientific computing in Python.

SciPy is an open-source scientific computing library for the Python programming language. Since its initial release in 2001, SciPy has become a de facto standard for leveraging scientific algorithms in Python, with over 600 unique code contributors, thousands of dependent packages, over 100,000 dependent repositories and millions of downloads per year. In this work, we provide an overview of the capabilities and development practices of SciPy 1.0 and highlight some recent technical developments

Using the cost-effectiveness of allogeneic islet transplantation to inform iPSC derived beta cell therapy reimbursement

In the present study a cost-effectiveness analysis of Allogeneic Islet Transplantation was performed and the financial feasibility of a Human Induced Pluripotent Stem Cell (hiPSC) derived Beta Cell therapy was explored. Previously published cost and health benefit data for Islet Transplantation was utilised to perform the cost-effectiveness and sensitivity analyses. It was determined that, over a 9 year time horizon, Islet Transplantation would become cost saving and ‘dominate’ the comparator. Over a 20 year time horizon, Islet Transplantation would incur significant cost savings over the comparator (£59,000). Finally, assuming a similar cost of goods to Islet Transplantation and a lack of requirement for immunosuppression, a hiPSC-derived Beta Cell therapy would dominate the comparator over an 8 year time horizon

Comparability of scalable, automated hMSC culture using manual and automated process steps

This is an open access article published by Elsevier under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Automation will likely to play a key role in the development of scalable manufacturing processes for cell-based therapies. In this study, we have compared the effects of manual centrifugation and automated non-centrifugation cell culture process steps, performed using TAP biosystems’ CompacT SelecT automated cell culture platform, upon hMSC morphology, number, viability, surface marker expression, Short tandem repeat (STR) profile, and paracrine function. Furthermore, the comparability between flow cytometry analyses of hMSCs, performed at multiple sites, was investigated. No significant difference in hMSC growth and characteristics was observed between cells cultured using either the manual centrifugation process step or the automated non-centrifugation process step, in which residual dissociation agent is carried over. However, some variability in paracrine activity was observed between hMSCs cultured using alternative process steps. It is also apparent that differences in analytical methods can influence the inter-laboratory reproducibility of hMSC flow cytometry analysis, although differences in culture may also contribute to the variability observed in the expression of 2 of the 8 surface markers examined. This novel investigation into the effects of these two key process steps will help to improve the understanding of the influence of automated cell culture upon various cell culture parameters, as well as upon process comparability