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Expanding access to CAR T cell therapies through local manufacturing

Nature Biotechnology volume 41, pages 1698–1708 (2023)Cite this article

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Abstract

Chimeric antigen receptor (CAR) T cells are changing the therapeutic landscape for hematological malignancies. To date, all six CAR T cell products approved by the US Food and Drug Administration (FDA) are autologous and centrally manufactured. As the numbers of approved products and indications continue to grow, new strategies to increase cell-manufacturing capacity are urgently needed to ensure patient access. Distributed manufacturing at the point of care or at other local manufacturing sites would go a long way toward meeting the rising demand. To ensure successful implementation, it is imperative to harness novel technologies to achieve uniform product quality across geographically dispersed facilities. This includes the use of automated cell-production systems, in-line sensors and process simulation for enhanced quality control and efficient supply chain management. A comprehensive effort to understand the critical quality attributes of CAR T cells would enable better definition of widely attainable release criteria. To supplement oversight by national regulatory agencies, we recommend expansion of the role of accreditation bodies. Moreover, regulatory standards may need to be amended to accommodate the unique characteristics of distributed manufacturing models.

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Fig. 1: Distributed manufacturing models.
Fig. 2: Proposed centralized approvals of distributed models.
Fig. 3: Pathways for exemption and exclusion of products from market approval requirements.
Fig. 4: Distribution of FACT-compliant organizations in the United States.

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Authors and Affiliations

  1. Harvard-MIT Center for Regulatory Science, Harvard Medical School, Boston, MA, USA

    Magdi Elsallab

  2. Cellular Immunotherapy Program, Cancer Center, Massachusetts General Hospital, Boston, MA, USA

    Magdi Elsallab & Marcela V. Maus

  3. Harvard Medical School, Boston, MA, USA

    Magdi Elsallab & Marcela V. Maus

  4. Cancer Center, Massachusetts General Hospital, Boston, MA, USA

    Marcela V. Maus

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Correspondence to Marcela V. Maus.

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Competing interests

M.V.M. is an inventor on patents related to adoptive cell therapies, held by Massachusetts General Hospital (some licensed to ProMab) and the University of Pennsylvania (some licensed to Novartis). M.V.M. holds equity in 2Seventy Bio, Century Therapeutics, NexImmune, Oncternal and TCR2 and has served as a consultant for multiple companies involved in cell therapies. M.V.M. is on the board of directors of 2Seventy Bio. M.V.M. has received grant and/or research support from CRISPR Therapeutics, Kite Pharma, Servier and Novartis. M.E. declares no competing interests.

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Elsallab, M., Maus, M.V. Expanding access to CAR T cell therapies through local manufacturing. Nat Biotechnol 41, 1698–1708 (2023). https://doi.org/10.1038/s41587-023-01981-8

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