Hidden translation costs in cell and gene therapy manufacturing

Abstract

Ex vivo cell and gene therapies have demonstrated remarkable clinical efficacy, yet their widespread adoption remains constrained by the complexity and cost of translation and manufacture. Current development commonly progresses through different equipment architectures: standard tissue-culture systems for process development, integrated patient-scale systems for early clinical manufacture, and factory-integrated systems for high-volume commercial production. Each transition can require process re-optimization, comparability, validation, and technology transfer. This review examines emerging manufacturing technologies and system architectures from a systems-engineering perspective. Drawing on Quality by Design, it proposes Design for Translation (DfT) as a future equipment R&D objective: to develop closed and automated platforms that support multiplexed process development while allowing the same validated unit operation to be replicated for clinical manufacture and commercial scale-out. By preserving the relevant cell microenvironment, critical process parameters, control logic and, digital records throughout the product lifecycle, DfT seeks to reduce platform-change costs and improve the affordability and accessibility of ex vivo cell and gene therapies.