Chimeric antigen receptor–T cell therapy manufacturing: modelling the effect of offshore production on aggregate cost of goods

Richard P Harrison,Ezequiel Zylberberg,Simon Ellison,Bruce L Levine

doi:10.1016/j.jcyt.2019.01.003

Richard P Harrison, Ezequiel Zylberberg + Show 2 more

Open Access

https://doi.org/10.1016/j.jcyt.2019.01.003

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Abstract

Cell and gene therapies have demonstrated excellent clinical results across a range of indications with chimeric antigen receptor (CAR)–T cell therapies among the first to reach market. Although these therapies are currently manufactured using patient-derived cells, therapies using healthy donor cells are in development, potentially offering avenues toward process improvement and patient access. An allogeneic model could significantly reduce aggregate cost of goods (COGs), potentially improving market penetration of these life-saving treatments. Furthermore, the shift toward offshore production may help reduce manufacturing costs. In this article, we examine production costs of an allogeneic CAR-T cell process and the potential differential manufacturing costs between regions. Two offshore locations are compared with regions within the United States. The critical findings of this article identify the COGs challenges facing manufacturing of allogeneic CAR-T immunotherapies, how these may evolve as production is sent offshore and the wider implication this trend could have.

Highlights

The recent approval by the U.S Food and Drug Administration (FDA) of the first chimeric antigen receptor (CAR)ÀT cell therapies [1,2] marks a significant step toward the emergence of a new paradigm in cancer treatment
To study the efficacy of offshore CAR-T cell therapy manufacturing, we model the manufacturing process in four distinct geographies: Cambridge, Massachusetts (USA), Manchester, New Hampshire (USA), Monterrey, Nuevo Leon (Mexico) and Buenos Aires, Buenos Aires (Argentina)
Despite the evident challenges associated with transferring even simple processes between multiple sites [21], standardized production facilities and associated quality systems have been established by both cell and gene therapy developers and contract manufacturing organizations across continents

Summary

Introduction

The recent approval by the U.S Food and Drug Administration (FDA) of the first chimeric antigen receptor (CAR)ÀT cell therapies [1,2] marks a significant step toward the emergence of a new paradigm in cancer treatment. Because these therapies have only recently made their way out of investigational clinical trials, overall production volumes remain small and many questions on reimbursement have yet to be resolved [2]. CAR-T cell therapies have been manufactured in centralized facilities, with the patient’s apheresis product being transported either fresh or cryopreserved from the clinical facility to a manufacturing facility and back. This mode of production has been associated with high per-unit manufacturing costs, leading many to seek ways of containing key cost drivers, including ancillary materials, transportation and logistics and skilled labor [4]

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