Automation: what will the cell therapy laboratory of the future look like?

Abstract

With the recent successes of CAR-T cell therapies there has been a renewed interest in bioprocessing and the manufacturing facilities required to meet the demands. Increasing the scale of any process has potential risks as well as rewards. While the drive to automation is clear, there is a lot of debate on the strategy. The decision on whether and when to automate a particular step can have long-term consequences on the therapies' cost-of-goods (COGs) and their successes. Automating the most complex and error-prone steps of a process is thought to be the best alternative to manual processes. However, automation may not be possible or even recommended for all steps in a process. Here, we examine both the barriers and the advantages of automation. Additionally, a detailed discussion of automating the autologous CAR-T cell process will look at each step from collection to infusion, and discuss the current automation offerings and speculate on potential future process changes. Through application of process analytics, we can gain a deeper understanding of the processes' consistency and tailor automation to fit the process. New potency assays will improve manufacturing processes and ensure the delivery of a safe and effective product. These advancements will then shape the cell therapy laboratory of our future.

Short Time to Market and Forward Planning Will Enable Cell Therapies to Deliver R&D Pipeline Value

“…For cell GMP footprint, our experience indicates that a regional hub model can deliver lower COGS if early investment is made in closed/automated cell processing. 64 In addition, implementation of platform plug and play CMC processes, methods, and formulations across a portfolio of assets will expedite development timelines and impact value generation from cell therapies.…”

Manufacturing T cells in hollow fiber membrane bioreactors changes their programming and enhances their potency

“…Development of an automated and scalable manufacturing process is a critical step in the evolution of this field and could bring down the cost of cell therapies to a level that would be sustainable within the limited health care budgets of most nations. 24 The HFMBR is an excellent base for the development of a fully closed automated manufacturing device. The Terumo Quantum is automated HFMBR-based instrument that can be used to expand T cells; 25 , 26 however, there have been no published reports of successful in situ T cell engineering in the Quantum system.…”

Autologous Induced Pluripotent Stem Cell–Based Cell Therapies: Promise, Progress, and Challenges

“…Automation and closed systems are considered to be essential for realizing the long‐term commercial success of iPSC‐derived therapies because one of the primary bottlenecks is the inability to migrate the manufacturing process from a manual, high‐risk academic bench protocol to an industrial‐scale, GMP‐compliant manufacturing system operating in a “factory of the future” to be able to handle patient demand and confidently manage risks to continuity and sustainability. As commonly stated by manufacturing experts, the two main risks for a typical cell therapy process are human error and lack of process understanding (including understanding of CQAs), causing unexpected outcomes; both risks can be effectively managed by housing an evolved process in the appropriate closed, automated system (Leong, Nankervis, & Beltzer, 2019).…”