Article inspired by a Tapas and TECH Talks digital event with insights from customer collaborations. Experts were from Cytiva and CCRM.
This article discusses options for cell therapy process development and validation that minimize risks through quality control (QC), optimization, scaling, closing, automation, and assay development, all in order to prepare for successful commercial production.
Cell therapy scale-up strategies
To achieve commercial success, a developed process must be scalable and suitable for a manufacturing environment. The scaling strategy depends on the type of cell therapy. Allogeneic therapies are meant to serve many patients. This scaling strategy of traditional bioprocessing, such as monoclonal antibody therapy processes a seed-train approach is common, where you scale across systems, progressively increasing in size. For allogeneic cell therapies, in order to minimize sterility and handling risks in more precious patient derived cells, scaling within the same system is desirable. This can be done with low cell volumes, starting with batch feeding, and then ramping up feed and waste production rates with perfusion to progressively expand cells. Also, in contrast, autologous cell therapies are personalized for each patient, so the batch sizes are small. Autologous therapies use a scale-out strategy, where additional small bioreactors are added to increase production throughput.
Allogeneic processes can be optimized at scales from 100 mL to 2 L, and volumes up to 25 L can be achieved in Cytiva’s Xuri rocking bioreactors. Very large batch needs up to 2000 L can be met in Cytiva’s Xcellerex line of stirred-tank bioreactors. For autologous processes, the 0.5 to 5 L volume range is usually enough. Large-scale bioreactors can be used for other immunotherapy platforms that require feeder layers or stimulatory cell lines.
Modern scale-up strategies for CAR T cell manufacturing, specifically the expansion of suspension T cell cultures, are very amenable to transfer into bioreactors for expansion . This allows the use of single-use equipment with closed connections, preferably sterile, weldable tubing lines, as well as automated liquid handling and perfusion. These advantages greatly lower the risk and cost compared with manual, labor-intensive processing while minimizing operator manipulations.