Technology is the root cause of the cell and gene therapy sector’s manufacturing challenges, according to Ori Biotech CEO, Jason Foster, who points out that it is also the solution.
The commercial cell and gene therapy sector began in 2017 when the FDA approved Novartis’ blood cancer treatment, Kymriah. Since then the agency has approved a handful of other therapies—bluebird bio’s Zynteglo and Kite Pharma’s Yescarta being examples. Despite this, the sector is far from mature and standardized ways of manufacturing these products have yet to emerge.
Production technology is a stumbling block, notes Foster, who says, “The current lack of automation technology that can simultaneously address needs for flexibility at the early stages to develop processes and can also effectively scale to meet commercial demand.
“Some therapy developers have chosen to make process changes post-commercialization to address the issue of scaling, however this is suboptimal as it introduces the burden of demonstrating process comparability to regulators. Others just try to stick with their ‘academic process’ which results in variable quality, high cost of goods, and low volumes.”
For cell and gene therapy developers who set up their own manufacturing units, there are other technology related challenges, continues Foster.
“The significant capex requirement of building large >100K-square-foot cell and gene therapy manufacturing facilities is a major challenge, mainly due to the lack of process intensification allowable in GMP with the currently available technologies, the human resource requirements, and the variable nature of the incoming patient material to initiate the manufacturing process.
“The inherent centralization of this model makes products more expensive and increases logistics and vein-to-vein times, reducing access for patients.”
And increased timelines have consequences, Foster says, explaining “most commercial CAR-T processes take more than a week for manufacturing, plus time for QC testing and release. This long vein-to-vein time for patient treatments is creating situations where patients are unacceptably dying on waitlists.”
Viral vectors—hollow viruses that can be filled with genetic information—play a vital role in cell and gene therapy development and production. And this is a problem because vectors are complex and time consuming to produce. Plus, capacity is limited.
“One of the biggest issues facing commercially approved CAR-T products is securing a reliable and quality supply of viral vector for their manufacturing processes,” Foster tells GEN. “As it relates to scaling up production, viral vectors create a lot of constraints in GMP, which increase COGS as they must be tightly controlled to avoid cross contamination between products.”
However, efforts to find better ways of making and handling vectors by cell and gene therapy developers and the CDMOs that serve them—including Ori—show real promise.
“With good automation technology, like we have developed at Ori, you will use less of these very expensive and hard to source inputs in every process alongside shortening processing times and reducing COGS dramatically,” states Foster.
“In addition to our manufacturing platform technology, we see digital infrastructure from friends and partners like TrakCel, Benchling, L7, POMS, Autolomous, and others really pioneering the move to fully digital processes,” he continues. “There are also some interesting developments in the PAT space from companies like Ovizio and also transfection technologies from Avectas, Kytopen, and others are looking at new methodologies to do genetic reprogramming that doesn’t require viral vector to overcome some of these challenges.
“We also see tech enabled service providers like CTMC, National Resilience, ElevateBio, Lykan, and the Center for Breakthrough Medicine pioneering the use of these new technologies to improve and streamline processes.”
Ori partnered with the CTMC last September in a project focused on implement digitally enabled process discovery and automated manufacturing solutions for the cell therapies.
“It’s a collaborative partnership with key objectives designed to assess a novel CAR-T processes already ongoing in its program onto Ori’s platform to highlight technical feasibility,” explains Foster. “The partnership is designed to enhance delivery of autologous cell therapies starting with feasibility through first-in-human clinical studies and all the way to eventual scaled commercialization.”