Cell Therapy-Processing Economics: Small-Scale Microfactories as a Stepping Stone Toward Large-Scale Macrofactories

Abstract

Aim:Manufacturing methods for cell-based therapies differ markedly from those established for noncellular pharmaceuticals and biologics. Attempts to 'shoehorn' these into existing frameworks have yielded poor outcomes. Some excellent clinical results have been realized, yet emergence of a 'blockbuster' cellbased therapy has so far proved elusive. Materials & methods: The pressure to provide these innovative therapies, even at a smaller scale, remains. In this process, economics research paper, we utilize cell expansion research data combined with operational cost modeling in a case study to demonstrate the alternative ways in which a novel mesenchymal stem cell-based therapy could be provided at small scale. Results & Conclusions: This research outlines the feasibility of cell microfactories but highlighted that there is a strong pressure to automate processes and split the quality control cost-burden over larger production batches. The study explores one potential paradigm of cell-based therapy provisioning as a potential exemplar on which to base manufacturing strategy.

Scalable Manufacturing of Human Mesenchymal Stromal Cells in the Vertical‐Wheel Bioreactor System: An Experimental and Economic Approach

“…The costs of goods per dose obtained within the scope of this study ($11 000–$21 000) are within the range of costs of goods obtained in other MSC bioprocess modeling studies . Given that the final prices of commercially available ATMPs are in the range of $500–$850 000 per dose, interventions aimed at reducing the costs of goods per dose are key to ensure sustainability of cell based products under reimbursement constraints …”

“…The increase in total consumable costs in the microcarrier‐based culture poses challenges in the scalability supply and cost of consumables . Additionally, other challenges are related with the need to guarantee scalability of the proliferative benefits across higher volume platforms, and that quality attributes are maintained . Finally, a current bottleneck of scalability is the volumes handled by current DSP systems, for which DSP with microcarrier‐based systems is generally less effective than for planar technologies…”

Challenges in Clinical Development of Mesenchymal Stromal/Stem Cells: Concise Review

“…In this scenario, the mentioned MSCs biological factors (i.e., tissue source, donor variability) have to be accounted since they may have a profound impact on manufacturing processes due to the expansion potential of the cells that is directly tied to the cost of production. Many efforts have been focused on the development of novel expansion technologies, to meet the needs of substantial cell numbers and the creation of a robust cell bank to supply cells for large number of recipients . The introduction of bioreactors providing billions of cells with consistent product quality and reproducibility has been recently proposed with promising results.…”

Identification and Characterization of a Large Source of Primary Mesenchymal Stem Cells Tightly Adhered to Bone Surfaces of Human Vertebral Body Marrow Cavities

“…Even at this level of production, with presumed economies of scale, the cost of goods sold (COGS) per dose of MSC could exceed $100,000 [3]. A significant driver of manufacturing costs, which is amplified proportionately with lot size, is the need to replenish master cell banks (MCB) through isolation of MSC from new donors due to the limited volumes of tissues and fluids that can be safely obtained from healthy volunteers and the limited expansion potential of MSC isolated from each donor [5,6]. MSC are rare in all tissues, comprising, for instance, ~0.001-0.01% of total nucleated cells (TNC) in BM aspirates [7].…”