Modeling Biological and Economic Uncertainty on Cell Therapy Manufacturing: the Choice of Culture Media Supplementation

Abstract

To evaluate the cost-effectiveness of autologous cell therapy manufacturing in xeno-free conditions. Materials & methods: Published data on the isolation and expansion of mesenchymal stem/stromal cells introduced donor, multipassage and culture media variability on cell yields and process times on adherent culture flasks to drive cost simulation of a scale-out campaign of 1000 doses of 75 million cells each in a 400 square meter Good Manufacturing Practices facility. Results & conclusion: Passage numbers in the expansion step are strongly associated with isolation cell yield and drive cost increases per donor of $1970 and 2802 for fetal bovine serum and human platelet lysate. Human platelet lysate decreases passage numbers and process costs in 94.5 and 97% of donors through lower facility and labor costs. Cost savings are maintained with full equipment depreciation and higher numbers of cells per dose, highlighting the number of cells per passage step as the key cost driver.

Human Platelet Lysate as a Functional Substitute for Fetal Bovine Serum in the Culture of Human Adipose Derived Stromal/Stem Cells

“…Additionally, they and Blande et al noted that the size of individual ASCs was larger when cultured in FBS as compared to HPL [19,26,29]. Such observations are consistent with a recent cost analysis, which concluded that HPL is substantially more economical than FBS for clinical grade ASC expansion due to accelerated growth rates [14]. Comparable to the current analysis, Blande et al, Cholewa et al, and Naaijikens et al independently demonstrated that the immunophenotype of ASCs cultured in FBS and HPL is comparable; however, Naaijikens et al alone reported an increased intensity of the CD73, CD90, and CD166 surface antigens in the presence of HPL as compared to FBS [19,26,29].…”

“…While FBS has been an effective medium for cell culture, it does have several additional disadvantages beyond those relating to the risk of BSE contamination. First, FBS products introduce considerable cost to the manufacturing process relative to human platelet lysate due in part to reduced proliferation rates and the need for extended culture expansion periods [14]. Second, FBS use introduces xenoproteins that bind to isolated ASCs, thereby increasing the risk of immune rejection due to antibody development against surface protein complexes on the transplanted ASCs.…”

Bringing Stem Cell‐Based Therapies for Type 1 Diabetes to the Clinic: Early Insights from Bioprocess Economics and Cost‐Effectiveness Analysis

“…The bioprocess economics model was reported elsewhere for mesenchymal stem/stromal cells . Briefly, this model encompassed the expansion of PSC in vials from a working cell bank (WCB).…”

“…We previously reported a bioprocess economics model, extended here for the expansion and differentiation of PSCs into islet cells. The incorporation of a health economics model of T1D supports optimization of manufacturing and clinical effectiveness.…”

Bioprocess Economic Modeling: Decision Support Tools for the Development of Stem Cell Therapy Products

“…The latter can much more easily benefit from economies of scale, as well as rely on the selection of a small group of ideal donors, whose cells are particularly easy to expand or show increased therapeutic potential. The careful selection of donors can significantly decrease the cost of a given bioprocess by reducing the time taken to achieve its target cell number, which concomitantly minimizes operating costs and the consumption of key resources, as evidenced by some of the BEMs here reviewed [ 35 , 53 ]. Moreover, the added complexities of maintaining and processing hESCs and hiPSCs, versus HSCs and MSCs, translate into higher quality control and personnel qualification costs, increasing expenses even further.…”