“There is broad consensus that we need to automate and quickly in order for cell therapy manufacturing to become a viable industry, especially in the field of autologous cell therapies but also in the allogeneic space,” said Fabian Gerlinghaus, CEO of Cellares, summarizing a roundtable discussion he led at ISCT 2022: Defining the Future of Cell Therapy Automation.
He was joined in that forum by experts in the cell therapy manufacturing field: Timothy Moore, COO of Pact Pharma, Randy Schweickart, senior director of process technology development, Bristol Myers Squibb (BMS), and Olivier Cremoux from Staubli Robotics.
The specialists all agreed that the earlier a developer implements automation in its cell therapy manufacturing process the better.
If a pharma company is using a scalable cell therapy manufacturing platform from as early as the preclinical phase, market entry could be accelerated by 1-2 years, as the regulatory process becomes more streamlined, and there is less rework in the clinic, argued Gerlinghaus.
His company has developed an end-to-end, enclosed cell therapy manufacturing system called the Cell Shuttle.
There are three different types of automation in cell therapy manufacturing: point solutions, which are benchtop instruments that handle one unit operation for one patient at a time, end to end solutions that can fully automate cell therapy manufacturing from start to finish for one patient and other high throughput systems that can carry out end to end automation for many patients at the same time, said the Cellares lead.
“All of the commercially available cell therapies that are FDA-approved today rely entirely on point solution manufacturing - one cell therapy manufacturing unit, one patient at a time.
“While those point solutions provide a great deal of flexibility, they also lock developers into a manufacturing paradigm that is failure prone due to the operator errors that can occur, and also due to the manual open transfers of reagents from the consumable cartridge of one instrument to the consumable cartridge of the next instrument. As a result, there are very high failure rates, along with incredibly high manufacturing costs, with this approach,” explained Gerlinghaus.
Fully automated and high throughput cell therapy manufacturing systems are designed to solve these kinds of operational complexities - they can significantly lower the risk of process failure as automation eliminates operator error, and, because such factory-in- a-box systems are fully closed, the opportunities for contamination are removed, he said.
Cell therapy manufacturing processes can vary greatly, so when asked whether Cellares' end to end processing system can handle that lack of industry standardization, Gerlinghaus told BioPharma-Reporter:
“Flexibility has been the challenge for the field. The cell therapy manufacturing process of every developer is slightly different - that was one of the biggest unsolved issues in this industry - how do you build a fully automated cell therapy manufacturing platform that provides high throughput while offering the level of flexibility that is required to support all of these different cell therapy modalities, both autologous and allogeneic, CAR-T, TCR, NK and HSC workflows, and the reagents within each of those categories. Being able to overcome that hurdle is core to our value proposition and one of the biggest differentiating factors of our technology platform."
Modular hardware supports the cell therapy applications but the flexibility to customize this platform to a particular company’s process is down to purpose-built software, he said.
Cell Shuttle allows parallel production of thousands of cell therapy doses per month. The system produces up to 10 patient doses simultaneously, increasing typical manufacturing throughput by a factor of 10, said the California-based technology provider.
In contrast, it takes up to two weeks to produce a single cell therapy dose today, with around 50 manual processing steps and about 80 hours of touch time, said the firm.
“One of the biggest operational complexities is figuring out how to scale out, to manufacture not a few hundred doses per year but tens of thousands of patient doses per year per drugs, and it is via the throughput of this platform that we can address this problem," said Gerlinghaus.
The entire manufacturing process is automated in this factory-in-a-box – from starting material to fill-finish, he said.
The closed system reduces the footprint that is required in cleanrooms, lowering the per patient manufacturing cost by up to 70% for most cell therapy workflows, he said. It also accelerates and de-risks developers' expansion into new markets, with huge cost savings, as cell therapy companies can build much smaller facilities, he continued.
The platform also dramatically reduces the amount of human labor needed. “You don’t need to hire the same number of people, and that brings great advantages, because, as this is such a specialized field, the industry does not have huge access to trained personnel. The talent pool just isn’t big enough. You will also need to do way less training as most of the manufacturing process is fully automated.”
In addition, the technology brings down the process failure rates by about a factor of three, added Gerlinghaus.
Under Cellares' now closed Early Access Partnership Program (EAPP), the Fred Hutchinson Cancer Research Center provided insights into key manufacturing workflows for multiple cell therapies, among other relevant applications. Other EAPP participants included PACT Pharma and Poseida Therapeutics along with an undisclosed large pharma group.
The company anticipates market entry for its platform in early 2024.