Rapid advances in cell therapy have resulted in complex processes. As they move toward the clinic, manufacturers are attempting to scale up or scale out the processes using legacy equipment that often was designed for other purposes.
For manufacturers, this means transport cell cultures from instrument to instrument. Much of the work is still manual, which delays optimal timelines and comes with risks or contamination, cell stress, and cell loss. For payers and patients, this means high price tags that put these specialized therapies out of reach.
The end-to-end automation that could address those needs of manufacturers, payers, and patients is still lacking in the commercial cell therapy processing sector. But, within the next few years, that can change.
“At Limula, we’re building a technology that can perform multiple steps, rather than use several technologies for each of the unique operations that must be performed in these complex processes,” Luc Henry, DPhil, CEO and co-founder, tells GEN from his office in Lausanne, Switzerland.
Its stand-alone LimONE cell therapy manufacturing solution is still in the phototype phase, but it makes it possible to go from lab- to commercial-scale in a closed, integrated, compact system. Scientists can take a cell therapy from discovery through manufacturing for a patient, all within one fully-automated processing device.
Limula took a ground-up, from scratch approach to design and achieved what Henry says is a first: the combination of a fermentation tank and centrifuge in a single technology. “Combining cell wash, cell processing, and formulation with the incubation steps, which are often linked to expansion and cell division, is something people have not seen before,” he continues. Cell therapy developers appear intrigued by the idea but, he admits, “We have a lot to prove.”
Luc Henry, DPhil, CEO and co-founder, Limula
Henry describes cell therapy manufacturing as a continuum between early process development, which requires the flexibility to explore many different parameters, and final production that may involve hundreds of doses for multiple patients.
The ability to keep cells in the same environment for scaleup eliminates many of the traditional challenges. Simply not transferring cells between tools reduces the risks of cell loss, cellular stress, contamination, lowers production costs, and increases product quality.
While Limula’s technology can scale up, out, and down, it also features another benefit: process intensification. The company achieves intensification by “automating and standardizing processes, to create scalability beyond what’s possible today,” Henry says. This means manufacturers can treat ten times more patients than they can today without increasing their cell processing footprint or staff. Because the processes and protocols are standardized, other facilities around the world can duplicate the production while maintaining a low learning curve.
In addition, LimONE features a high-density cell culture of eight million cells per mL for T cell cultures, in contrast to the one million cells per mL typically achieved by traditional processes. Such high density compensates for its relatively small, 500 mL, maximum useful volume of cell culture and makes it possible to use LimONE to produce therapeutic doses for patients.
Limula’s LimONE functional prototype was delivered to CDMO partner Stemmatters in Portugal last month for beta testing, with three more devices planned for delivery from September onwards. “Cell incubation data is being released now that shows the technology can perform operations around cell activation and transfection,” which are necessary for successful gene transfer and expansion steps. “We’ve shown it performs as well as the best-in-class bioreactors,” Henry says.
“Now we want to show we can do that in fully automated sequences, together with the wash and formulation at the beginning and end of the process.” He says he expects this technology to be commercially available, “in a couple of years.”
So far, this cell processing solution has been used primarily to develop T-cell therapeutics because those are most common in cell therapy. Therapies using other cell types, including NK cells and hematopoietic stem cells, are being explored with partnerships at clinical centers, biotech companies, and contract research and development organizations.
“We want to focus on relatively low-scale manufacturing,” explains Henry. “Autologous cell therapies (which are made for individual patients) are our sweet spot.”
While some may consider low production volumes a limitation, Henry positions it as an advantage. With a dynamic volume that can range from 2 mL to 500 mL— “much larger than other technologies” he notes—LimONE can handle not only the larger cell culture volumes needed to treat patients, but also the small volumes of cells used during the discovery process.
To further support scale down, Limula has a simple, non-GMP, model of the technology that lets developers model the process and develop the therapeutic recipe at a small scale. “This is simple enough to use to develop early-stage processes, maximize flexibility, and learn how the technology behaves on your system,” he says. Once that’s perfected, researchers can port it to the automated platform “without changing the container where the cells are manipulated.”
That capability is novel, he says, noting that tech transfer historically has been beset by challenges in the transfer from the lab-to-commercial-scale parallel or multiplex processing systems.
When using LimONE, Henry points out, “The material is the same, and the form factor and scale are the same,” which streamlines the tech transfer process. “This is why we think it will be appropriate both for clinical centers that will manufacture 100 doses per year and also for biopharma companies that need a much larger production capacity.”
The design was developed based upon feedback from nearly two dozen goal management training (GMT) operators from both industry and academia to ensure it met the needs of both groups of future users. “We’re showing our technology to a lot of people to get as much feedback as possible,” Henry says
In developing this automated cell therapy processing platform, Limula’s founders aim to create a production technology that is so disruptive that cell therapy will be available and affordable for any patient who needs it.
The post Limula’s End-to-End Cell Processing Platform Enters Beta Testing appeared first on GEN - Genetic Engineering and Biotechnology News.
For manufacturers, this means transport cell cultures from instrument to instrument. Much of the work is still manual, which delays optimal timelines and comes with risks or contamination, cell stress, and cell loss. For payers and patients, this means high price tags that put these specialized therapies out of reach.
The end-to-end automation that could address those needs of manufacturers, payers, and patients is still lacking in the commercial cell therapy processing sector. But, within the next few years, that can change.
“At Limula, we’re building a technology that can perform multiple steps, rather than use several technologies for each of the unique operations that must be performed in these complex processes,” Luc Henry, DPhil, CEO and co-founder, tells GEN from his office in Lausanne, Switzerland.
Its stand-alone LimONE cell therapy manufacturing solution is still in the phototype phase, but it makes it possible to go from lab- to commercial-scale in a closed, integrated, compact system. Scientists can take a cell therapy from discovery through manufacturing for a patient, all within one fully-automated processing device.
Ground-up approach
Limula took a ground-up, from scratch approach to design and achieved what Henry says is a first: the combination of a fermentation tank and centrifuge in a single technology. “Combining cell wash, cell processing, and formulation with the incubation steps, which are often linked to expansion and cell division, is something people have not seen before,” he continues. Cell therapy developers appear intrigued by the idea but, he admits, “We have a lot to prove.”
Luc Henry, DPhil, CEO and co-founder, Limula
Henry describes cell therapy manufacturing as a continuum between early process development, which requires the flexibility to explore many different parameters, and final production that may involve hundreds of doses for multiple patients.
The ability to keep cells in the same environment for scaleup eliminates many of the traditional challenges. Simply not transferring cells between tools reduces the risks of cell loss, cellular stress, contamination, lowers production costs, and increases product quality.
While Limula’s technology can scale up, out, and down, it also features another benefit: process intensification. The company achieves intensification by “automating and standardizing processes, to create scalability beyond what’s possible today,” Henry says. This means manufacturers can treat ten times more patients than they can today without increasing their cell processing footprint or staff. Because the processes and protocols are standardized, other facilities around the world can duplicate the production while maintaining a low learning curve.
In addition, LimONE features a high-density cell culture of eight million cells per mL for T cell cultures, in contrast to the one million cells per mL typically achieved by traditional processes. Such high density compensates for its relatively small, 500 mL, maximum useful volume of cell culture and makes it possible to use LimONE to produce therapeutic doses for patients.
Spring beta tests
Limula’s LimONE functional prototype was delivered to CDMO partner Stemmatters in Portugal last month for beta testing, with three more devices planned for delivery from September onwards. “Cell incubation data is being released now that shows the technology can perform operations around cell activation and transfection,” which are necessary for successful gene transfer and expansion steps. “We’ve shown it performs as well as the best-in-class bioreactors,” Henry says.
“Now we want to show we can do that in fully automated sequences, together with the wash and formulation at the beginning and end of the process.” He says he expects this technology to be commercially available, “in a couple of years.”
So far, this cell processing solution has been used primarily to develop T-cell therapeutics because those are most common in cell therapy. Therapies using other cell types, including NK cells and hematopoietic stem cells, are being explored with partnerships at clinical centers, biotech companies, and contract research and development organizations.
“We want to focus on relatively low-scale manufacturing,” explains Henry. “Autologous cell therapies (which are made for individual patients) are our sweet spot.”
While some may consider low production volumes a limitation, Henry positions it as an advantage. With a dynamic volume that can range from 2 mL to 500 mL— “much larger than other technologies” he notes—LimONE can handle not only the larger cell culture volumes needed to treat patients, but also the small volumes of cells used during the discovery process.
To further support scale down, Limula has a simple, non-GMP, model of the technology that lets developers model the process and develop the therapeutic recipe at a small scale. “This is simple enough to use to develop early-stage processes, maximize flexibility, and learn how the technology behaves on your system,” he says. Once that’s perfected, researchers can port it to the automated platform “without changing the container where the cells are manipulated.”
That capability is novel, he says, noting that tech transfer historically has been beset by challenges in the transfer from the lab-to-commercial-scale parallel or multiplex processing systems.
When using LimONE, Henry points out, “The material is the same, and the form factor and scale are the same,” which streamlines the tech transfer process. “This is why we think it will be appropriate both for clinical centers that will manufacture 100 doses per year and also for biopharma companies that need a much larger production capacity.”
The design was developed based upon feedback from nearly two dozen goal management training (GMT) operators from both industry and academia to ensure it met the needs of both groups of future users. “We’re showing our technology to a lot of people to get as much feedback as possible,” Henry says
In developing this automated cell therapy processing platform, Limula’s founders aim to create a production technology that is so disruptive that cell therapy will be available and affordable for any patient who needs it.
The post Limula’s End-to-End Cell Processing Platform Enters Beta Testing appeared first on GEN - Genetic Engineering and Biotechnology News.