Patient-Specific Supply Chains: Off the Shelf or Made from Scratch?

The significant majority of approved patient-specific therapies are following a cyclic supply chain pattern, according to which key therapy raw materials (usually cells) are donated from the patients themselves. Such an example are autologous Chimeric Antigen Receptor T (CAR T) cell therapies that bring a novel perspective in cancer treatment [1], [2], [3]. Their patient-centric nature makes CAR T cells a unique class of therapy to manufacture and distribute. The latter is associated with significant challenges that arise from the central role that patient schedule plays in the supply chain.

Allogeneic CAR T cell therapies could be a robust alternative to their autologous counterpart as the main raw material (cells) can be off-the-shelf, as it is provided in advance by a compatible donor. This can alleviate risks associated to highly distributed upstream of the supply chain and lead to decreased transport/storage risks. Although no allogeneic CAR T formulation is available yet, a potential approval of such therapies could create a step change in personalised treatments. In this work, we develop Mixed Integer Linear Programming (MILP) models to compare allogeneic and autologous CAR T cell therapy supply chain networks. We investigate different network configurations with increased level of distribution, and we assess their performance with respect to: (a) cost, (b) scalability and (c) total return time of the therapy.

Acknowledgments

Funding from the UK Engineering & Physical Sciences Research Council (EPSRC) for the Future Targeted Healthcare Manufacturing Hub hosted at University College London with UK university partners is gratefully acknowledged (Grant Reference: EP/P006485/1). Financial and in-kind support from the consortium of industrial users and sector organisations is also acknowledged.

References

[1] Novartis, “KYMRIAH Treatment Process, Dosing & Administration | HCP,” 2018. [Online]. Available: https://www.hcp.novartis.com/products/kymriah/acute-lymphoblastic-leukemia-children/dosing-and-administration/. [Accessed: 07-Mar-2019].

[2] Kite Pharma, “First CAR T Therapy for Certain Types of Relapsed or Refractory B-Cell Lymphoma,” 2018. [Online]. Available: https://www.yescartahcp.com/. [Accessed: 07-Mar-2019].

[3] B. L. Levine, J. Miskin, K. Wonnacott, and C. Keir, “Global Manufacturing of CAR T Cell Therapy,” Mol. Ther. - Methods Clin. Dev., vol. 4, no. March, pp. 92–101, 2017.