Cell therapy production processes tend to evolve as the product moves through clinical development towards approval. While such changes may streamline testing, they can be a challenge when it comes to commercial scale-up.
Production processes for T-cell based therapies can be difficult to scale up according to Trevor Smith, senior marketing manager at technology supplier Terumo’s cell and gene therapy business.
“One of the technical challenges during scale up is that the process developed to manufacture trial supplies is almost always different from the final process required for commercialization,” he told GEN, explaining that the focus is getting into trials quickly, rather than scalability.
“As a result, positive clinical trial results mean developers must ‘double back to more scalable solutions, which can change the culture vessel, materials of contact, and even the media and reagents used to varying degrees.”
“This variability must be addressed to move forward, which adds complexity to scaling up,” Smith said.
Another factor is the lack of standardization, he continued, adding that, “cell therapy manufacturing processes are still very much bespoke in nature, so no clear ‘standard approach’ has emerged.”
“I would say that while some consolidation may appear in the space, there likely won’t be a ‘one size fits all’ approach based on the personalized nature of these therapies and the unique needs to each modality.
“What will support scale up, however, is the adoption of automated platforms earlier in the process—while costs may be initially high, the value of taking that step saves time in the long run on the path to commercialization,” Smith said.
Avoiding variability
Earlier this month Terumo partnered with Fujifilm Irvine Scientific to develop a T-cell expansion platform that cell therapy firms can use to streamline commercial scale-up.
The idea is to jointly offer developers production technologies that can be used during each phase of product development, thereby providing a consistency that will streamline scale-up, Smith said.
“For instance, Fujifilm Irvine Scientific offers chemically defined formulations, as well as xeno- and serum-free media, to assist in satisfying the most stringent regulatory requirements.
“Similarly, Terumo Blood and Cell Technologies Quantum Flex is a GMP device, but has a scaled down and scaled up bioreactor with identical materials of contact along the fluid path, avoiding variability as you move from small to standard.”
The combined effort builds on an existing relationship that has seen Terumo use Fujifilm’s media in research, notably the work on rapid CAR-T expansion published in November last year.
Smith cited this as a positive for cell therapy developers, explaining, “Much of Terumo’s publicly facing data sets Fujifilm’s media. This is convenient, as end users can see different protocols with proven results to help them adopt both solutions in their own process.”
