Ethical Considerations in the Manufacturing of Personalized Cell and Gene Therapies

Ashleigh Henning – Georgia Institute of Technology; Adwik Rahematpura – Georgia Institute of Technology; Yizhe Wang – Georgia Institute of Technology

Abstract: In recent years, several novel combined cell and gene therapies have gained market access in the United States and around the world. These therapies offer remarkable promise to benefit, or even cure, patients with certain genetic diseases or hematologic malignancies. Yet the extended and distributed manufacturing process associated with these therapies raises challenging and under-explored ethical concerns. In this presentation, we will draw on the results of a systematic analysis of the first six chimeric antigen receptor T (CAR-T) cell therapies approved by the U.S. Food and Drug Administration. Briefly, we have developed product narratives for these six therapies through a review of a wide array of publicly available data (e.g., company documents, SEC filings, media coverage,, etc.). We draw on these product narratives, using a comparative case study approach, to identify key ethical issues that arise due to the nature of the personalized cell therapy manufacturing process. Key issues identified include how best to allocate scarce manufacturing capacity to patients, how to proceed when a manufacturing error occurs, a dose fails to meet release criteria, or a patient’s health status changes during manufacturing. We illustrate these ethical considerations with specific examples, drawing on relevant ethical principles and examining tradeoffs. We conclude by identifying areas where policy development, either at the level of the individual company or manufacturing facility or, in an industry-wide manner, by national regulatory or reimbursement bodies, could help address these issues and support the successful commercialization of personalized cell and gene therapies.

Keywords: Personalized medicine, Cell and gene therapy, Manufacturing