De-risking cell therapy manufacturing with downstream technology innovation
"However, there are limited automated solutions in this area, much less specific to formulation, fill, and finish, that genuinely address the market needs," Kathie Schneider, director, global commercial lead, and Dalip Sethi, director, scientific affairs, Terumo BCT, told us.
Terumo Blood and Cell Technologies (BCT), a US-based medical technology firm and subsidiary of Tokyo-based Terumo Corporation, has been focusing on innovation in downstream technologies to automate the final steps involved in autologous cell therapy manufacturing.
Final formulation is considered one of the most critical steps in the autologous cell therapy manufacturing process but many developers are still performing this process manually, they said.
"To get drug products to scale in manufacturing, automation is required. Solutions must maintain the viability of the product as much as possible so that the cells are able to proliferate inside the body. This is further complicated with autologous products; one product is one batch. Therefore, finding automated solutions can be a challenge due to the smaller batch sizes.
"Uniquely maintaining drug products at ultralow temperatures, that can maintain the products viability from the fill/finish stage through infusion is also a challenge. The complex final formulation steps involve the addition of pre-cooled cryoprotectants and maintaining the cell product at low temperature for a short duration before freezing, which can limit the batch size of the drug product."
Limitations of manual approaches
In the addition of pre-cooled cryoprotectants, cells are mixed with dimethyl sulfoxide (DMSO) and that process needs to be managed very carefully so as not to harm the cells, via slow addition with chill plates, said the Terumo team.
“Managing the DMSO addition, accurately aliquoting into specific bags, sealing the bag, and maintaining batch records leave opportunities for errors. With manual processes, we have found customers lose cell viability, experience operator-related product variability, experience contamination due to open events, and errors in data logging.”
Terumo’s automated Finia system, made available to the market in 2020, addresses this final step.
“The Finia system automatically adjusts product temperature, as per user’s protocol, with the mixing and cooling assembly for cells, buffer, and DMSO. The system accurately aliquots the desired volume across three product bags plus a QC bag. Finally, the system removes air, seals the product bags for downstream, cryopreservation, and logs the steps for export into batch records, thus making this process much more scalable as manufacturers manage increased patient volume.
“Terumo found that in this process, the product maintained >90% post-thaw cell viability. Finia hands-on time is typically 6.4 minutes versus 56.7 minutes when performed manually.”