A risk-based approach for cell line development, manufacturing and characterization of genetically engineered, induced pluripotent stem cell-derived allogeneic cell therapies

Advances in cellular reprogramming and gene-editing approaches have opened up the potential for a new class of ex vivo cell therapies based on genetically engineered, induced pluripotent stem cell (iPSC)-derived allogeneic cells. While these new therapies share some similarities with their primary cell-derived autolo-gous and allogeneic cell therapy predecessors, key differences exist in the processes used for generating genetically engineered, iPSC-derived allogeneic therapies. Specifically, in iPSC-derived allogeneic therapies, donor selection and gene-editing are performed once over the lifetime of the product as opposed to as part of the manufacturing of each product batch. The introduction of a well-characterized, fully modified, clonally derived master cell bank reduces risks that have been inherent to primary-cell derived autologous and allo-geneic therapies. Current regulatory guidance, which was largely developed based on the learnings gained from earlier generation therapies, leaves open questions around considerations for donor eligibility, starting materials and critical components, cell banking and genetic stability. Here, a risk-based approach is proposed to address these considerations, while regulatory guidance continues to evolve.(c) 2022 International Society for Cell & Gene Therapy. Published by Elsevier Inc. This is an open access articleunder the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Automated summary

Advances in cellular reprogramming and gene-editing have provided potential for ex vivo cell therapies based on genetically engineered iPSC-derived allogeneic cells. There are differences in the processes used for generating these therapies compared to primary cell-derived autologous and allogeneic therapies. Regulatory guidance needs to address considerations such as donor eligibility, starting materials, cell banking, and genetic stability.