Ioannis Papantoniou, Toon Lambrechts & Jean-Marie Aerts
Overcoming downstream bottlenecks in cell and gene therapy manufacturing
Autologous cell therapies are currently being evaluated in multiple clinical trials and are becoming a reality in advanced healthcare services. Compared to allogeneic cell therapies, where one batch of cells can be used to treat multiple patients and which allows a business model that is more closely related to the traditional biologics, autologous or patient-specific cell-based therapies present a whole new set of challenges. While these new challenges can originate from ethical issues (e.g., concerns about the patient in cases of batch failure) or from safety concerns (e.g., cross-contamination between patients), this article provides an overview of the technical side of cell-therapy manufacturing that is subject to donor-related variability. Although several studies have managed to produce batches of cells with a scale that satisfies therapeutic needs, there are still a number of challenges that need to be tackled. Unlike traditional manufacturing processes where the input material is relatively constant over time, personalization aspects inherent to the autologous reality will expose manufacturing to significant variability and production risks. The authors argue that for autologous cell production, where every patient-specific production batch can be considered as an unknown process, a combination of automated production processes and robust process monitoring & control capabilities can provide quantitative process understanding. At a second stage, provided large data becomes available through (on-line) data-based process analytics, minimized risk and cost-effective cell production for clinical use will become a reality.
Submitted for review: May 19 2017 Published: Aug 4 2017
Citation: Cell Gene Therapy Insights 2017;3(6), 469-482.