As cell therapy processes mature and advance further beyond clinical trials, the shift to the manufacture and supply of affordable therapies will become more important.
These therapies are expensive. High cost of goods (COGs) can be a cause of commercial failure with cell therapies, so manufacturing processes and logistics need to be considered, along with clinical science, from the beginning[i].
Given the labour-intensity of these processes, the current trend is to automate to reduce costs. Several automated systems are currently available for cell therapy applications that enable automated cell isolation and washing, or fully integrated platforms that can be used for programmable automated cell separation, washing, expansion and concentration. However, depending on the process, automation may or may not be the solution. Biosolve Process modelling software has recently been used to evaluate the impact of two different degrees of automation in autologous cell therapy processing. Surprisingly the results show that the introduction of fully automated platforms did not necessarily result in a reduction of cost of therapy per patient[ii],[iii],[iv]. The cell expansion phase, post transduction, is a bottleneck which ties up the fully automated system, so partial automation was more attractive option. Besides labour, the costs associated with viral vectors (used for gene introduction of CARs) and the costs of QC tests were found to have the most significant impact on the final cost of therapy. In these cases, the decision on whether to outsource these activities or perform them in-house becomes important.
In an expanded study, BioSolve Process was used to model, develop and optimise the wider supply chain as a cell therapy process.. This is particularly relevant for commercial autologous CAR-T therapies with future demand of >10,000 patients per year. Both centralised manufacturing (as currently practised for Kymriah and Yescarta) and local manufacturing can be modelled and compared for efficiency, capacity, risk and cost.
Biosolve Process has also been used for the economic analysis of allogenic cell therapies, particularly for the production of allogeneic Mesenchymal Stem Cell (MSC) therapy[v]. Here, automated systems and bag culture systems were incorporated into Biosolve to reflect current specific process requirements. Interestingly, this study also considered the significant impact of Umbilical Cord Blood (UCB) starting material collection and acquisition upon the final cost of therapy.
We at Biopharm Services have been supporting the Cell and Gene Therapy bioprocessing community in providing insights into the process efficiency of automation and supply chain routes of both autologous and allogeneic cell therapies. To this end we have enhanced the capabilities of Biosolve Process to incorporate typical laboratory equipment, materials and consumables such as incubators, bench-top centrifuges, controlled rate freezers, among others, as well as centrifuge tubes, shake flasks, etc.. These items are not usually considered manufacturing scale equipment, but cell therapy presents challenges not faced by traditional biologics manufacturing.
We look forward to continued interactions with our CGT clients to optimize delivery of these effective therapeutics.
[i] Orchard-Webb D. Progress toward commercial scale and efficiency in cell therapy bioprocessing. BioProcess Int. (2016) 14:8–17. https://bioprocessintl.com/wp-content/uploads/2016/10/14-9-sup-OrchardWebb.pdf
[ii] Lopes AG, A. Sinclair, Frohlic B. Cost Analysis of Cell Therapy Manufacture – Autologous Cell Therapies, Part 1. Bioprocess Int 2018; 16(3)i, 3-15. https://bioprocessintl.com/manufacturing/cell-therapies/analysis-cost-of-cell-therapy-manufacturing-autologous-cell-therapies-part-1/
[iii] Lopes AG, Sinclair A, Frohlic B. Cost Analysis of Cell Therapy Manufacture – Autologous Cell Therapies, Part 2. Bioprocess Int 2018; 16(4), 12-19. https://bioprocessintl.com/manufacturing/cell-therapies/cost-analysis-of-cell-therapy-manufacturing-autologous-cell-therapies-part-2/
[iv]A.G. Lopes, R. Noel, A. Sinclair. Cost Analysis of Vein-to-vein CAR T-Cell Therapy: Automated Manufacturing and Supply Chain. Cell and Gene Therapy Insights Journal, 2020 (in press)
[v] Torres-Acosta, Mario A., Richard P. Harrison, Elizabeth Csaszar, Marco Rito-Palomares, and Marion E. G. Brunck. “Ex Vivo Manufactured Neutrophils for Treatment of Neutropenia—A Process Economic Evaluation.” Frontiers in Medicine 6 (2019). https://doi.org/10.3389/fmed.2019.00021.