Abstract
Stem cell therapies are promising for diverse indications. However, there are manufacturing and reimbursement challenges that must be addressed toward widespread adoption. Relying on bioprocess and/or health economics models, early health technology assessment (eHTA) has provided insights on manufacturing innovations towards reducing the manufacturing cost of goods (CoG), and the long-term value that prospective stem cell therapies must provide to secure reimbursement. These economics models have focused on commercial tools or proprietary code. In order to increase awareness to the usefulness of eHTA in stem cell engineering, this thesis presents a new open-source tool, TESSEE (Tool for Early Stem Cells Economic Evaluation). Three relevant case studies for mesenchymal stem/stromal cell (MSC) and pluripotent stem cell (PSC) based therapies are presented as applications of TESSEE for decision-making in the implementation of stem cell engineering innovations. A study on the choice of a culture media supplement for autologous MSC therapy manufacturing determined that human platelet lysate (hPL) reduces CoG, in comparison to fetal bovine serum (FBS), for 97% of donors. An expansion system focused case study showed that the implementation of a new vertical wheel reactor (VWR) for the microcarrier-based culture of MSC increases the number of cells per batch and reduces costs of goods per dose by up to 48% from typical two-dimensional flasks for expansion. eHTA of devices containing PSC-derived beta cells for treatment of type 1 diabetes patients showed that the transplantation of the devices could be very effective at improving the quality of life. However, a price reduction, accompanied by reduction of manufacturing costs, is required to achieve widespread cost-effectiveness. This thesis highlights the versatility of TESSEE and builds evidence for eHTA for rational implementation of innovations in stem cell engineering, towards more cost-effective stem cell therapies.
Research supported by Fundação para a Ciência e Tecnologia (FCT) through the PhD Fellowship PD/BD/105868/2014.
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References
Shukla, V., Seoane-Vazquez, E., Fawaz, S., Brown, L.M., Rodriguez-Monguio, R.: The landscape of cellular and gene therapy products: cost, approvals, and discontinuations. Hum. Gene Ther. Clin. Dev., April 2019. humc.2018.201
Home - ClinicalTrials.gov. https://clinicaltrials.gov/. Accessed 03 Jul 2019
Simaria, A.S., et al.: Allogeneic cell therapy bioprocess economics and optimization: single-use cell expansion technologies. Biotechnol. Bioeng. 111(1), 69–83 (2014)
Ikebe, C., Suzuki, K.: Mesenchymal stem cells for regenerative therapy: optimization of cell preparation protocols. Biomed. Res. Int. 2014, 951512 (2014)
Mizukami, A., et al.: Technologies for large-scale umbilical cord-derived MSC expansion: experimental performance and cost of goods analysis. Biochem. Eng. J. 135, 36–48 (2018)
Banta, D.: The development of health technology assessment. Health Policy 63(2), 121–132 (2003)
Ijzerman, M., Wissing, T., de Koning, E.: Early health economic evaluation of bioartificial organs: involving users in the design of the bioartificial pancreas for diabetes. In: Stamatialis, D. (ed.) Biomedical Membranes and (Bio)artificial Organs. World Scientific Publishing Co. Pte Ltd., New Jersey (2017)
de Windt, T.S., Sorel, J.C., Vonk, L.A., Kip, M.M.A., Ijzerman, M.J., Saris, D.B.F.: Early health economic modelling of single-stage cartilage repair. Guiding implementation of technologies in regenerative medicine. J. Tissue Eng. Regen. Med. 11(10), 2950–2959 (2017)
Wallner, K., et al.: Stem cells and beta cell replacement therapy: a prospective health technology assessment study. BMC Endocr. Disord. 18(1), 6 (2018)
Jenkins, M., Bilsland, J., Allsopp, T.E., Ho, S.V., Farid, S.S.: Patient-specific hiPSC bioprocessing for drug screening: bioprocess economics and optimisation. Biochem. Eng. J. 108, 84–97 (2016)
Weil, B.D., et al.: An integrated experimental and economic evaluation of cell therapy affinity purification technologies. Regen. Med. 12(4), 397–417 (2017)
Pereira Chilima, T.D., Moncaubeig, F., Farid, S.S.: Impact of allogeneic stem cell manufacturing decisions on cost of goods, process robustness and reimbursement. Biochem. Eng. J. 137, 132–151 (2018)
Hassan, S., Simaria, A.S., Varadaraju, H., Gupta, S., Warren, K., Farid, S.S.: Allogeneic cell therapy bioprocess economics and optimization: downstream processing decisions. Regen. Med. 10(5), 591–609 (2015)
Harrison, R.P., Medcalf, N., Rafiq, Q.A.: Cell therapy-processing economics: small-scale microfactories as a stepping stone toward large-scale macrofactories. Regen. Med. 13(2), 159–173 (2018)
Darkins, C.L., Mandenius, C.-F.: Design of large-scale manufacturing of induced pluripotent stem cell derived cardiomyocytes. Chem. Eng. Res. Des. 92(6), 1142–1152 (2014)
Placzek, M.R., et al.: Stem cell bioprocessing: fundamentals and principles. J. R. Soc. Interface 6(32), 209–232 (2009)
Sampson, C.J., et al.: Transparency in decision modelling: what, why, who and how? Pharmacoeconomics, pp. 1–15, June 2019
TESSEE - Tool for Early Stem cellS Economic Evaluation Source Code. https://github.com/catiabandeiras/TESSEE. Accessed 10 Jul 2019
Bandeiras, C., Cabral, J.M., Finkelstein, S.N., Ferreira, F.C.: Modeling biological and economic uncertainty on cell therapy manufacturing: the choice of culture media supplementation. Regen. Med. 13(8), 917–933 (2018)
Sousa Pinto, D., et al.: Scalable manufacturing of human mesenchymal stromal cells in the vertical-WheelTM bioreactor system: an experimental and economic approach. Biotechnol. J., p. 1800716, April 2019
Bandeiras, C., Cabral, J.M.S., Gabbay, R.A., Finkelstein, S.N., Ferreira, F.C.: Bringing stem cell-based therapies for type 1 diabetes to the clinic: early insights from bioprocess economics and cost-effectiveness analysis. Biotechnol. J., p. 1800563, May 2019
Faulkner, S., et al.: Pricing and reimbursement experiences and insights in the European Union and the United States: Lessons learned to approach adaptive payer pathways. Clin. Pharmacol. Ther. 100(6), 730–742 (2016)
Sutton, M.T., et al.: Antimicrobial properties of mesenchymal stem cells: therapeutic potential for cystic fibrosis infection, and treatment. Stem Cells Int. 2016, 1–12 (2016)
Bandeiras, C., Koc, J.R., Ma, Y., Samberg, M., Finkelstein, S., Ferreira, F.: Cost effectiveness analysis of allogeneic, just-in-time expansion of mesenchymal stem cells with PLUSTM human platelet lysate for a clinical trial. Cytotherapy 20(5), S60 (2018)
Bandeiras, C., Cabral, J.M.S., Finkelstein, S.N., Ferreira, F.C.: Logical process designs for stem cell manufacturing: computational support tools for improved cost-effectiveness. RegMedNet (2017). https://www.regmednet.com/users/3641-regmednet/posts/19843-logical-process-designs-for-stem-cell-manufacturing-computational-support-tools-for-improved-cost-effectiveness
ICER - Institute for Clinical and Economic Review. https://icer-review.org/. Accessed 10 Jul 2019
Innovation and Value Initiative. https://www.thevalueinitiative.org/. Accessed 10 Jul 2019
Acknowledgment
The authors acknowledge funding from Institute for Bioengineering and Biosciences (UID/BIO/04565/2013) and Programa Operacional Regional de Lisboa 2020 (Project No. 007317) and also through the project PRECISE (PAC-PRECISE-LISBOA-01-0145-FEDER-016394). C. Bandeiras also acknowledges the support from the MIT Portugal Program in Bioengineering, namely through the research stays in the Institute for Data, System and Society – MIT and the Division of Clinical Informatics, Beth Israel Deaconess Medical Center, Harvard Medical School.
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Bandeiras, C., Sampaio Cabral, J.M., Finkelstein, S.N., Ferreira, F.C. (2020). TESSEE – Tool for Early Stem Cells Economic Evaluation. In: Henriques, J., Neves, N., de Carvalho, P. (eds) XV Mediterranean Conference on Medical and Biological Engineering and Computing – MEDICON 2019. MEDICON 2019. IFMBE Proceedings, vol 76. Springer, Cham. https://doi.org/10.1007/978-3-030-31635-8_233
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