Automated and Manual Cell Expansion Analysis Shows Statistical Equivalence

Multiply Labs, a robotics firm developing automated manufacturing systems to produce individualized drugs, reported performance results for its proof-of-concept robotic system, developed along with UCSF, Cytiva, Thermo, Fisher Scientific, and Charles River Laboratories.

The data demonstrate that automated cell therapy manufacturing outcomes (cell quantity and quality) using Multiply Labs’ robotic system are statistically equivalent to that of a process performed manually, according to Multiply Labs officials. Given this robotic technology is compatible with leading cell therapy manufacturing instruments, the data indicate that it is possible to automate an existing cell expansion protocol without significantly changing the process or impacting product characteristics, noted Fred Parietti, PhD, co-founder and CEO of Multiply Labs.

The research, titled “Development of a robotic cluster for automated and scalable cell therapy manufacturing,” is currently under review. You can read the full preprint here.

“We are so excited by this initial data as it opens the door to accelerating the availability of cell therapies,” continued Parietti. “The data demonstrate that manufacturers can confidently automate their existing processes for cell expansion, without making significant modifications to the process itself, effectively minimizing bioprocess and regulatory risks. With this level of automation there is great potential to decrease labor costs and increase manufacturing throughput for these life-saving therapies.”

Assessing robotic system’s ability to culture T cells

To assess the robotic system’s ability to culture T cells, manual and robotic conditions were tested in parallel with three replicates each. For both conditions, human T cells were activated and placed into a small-scale bioreactor in a cell culture incubator. After seven days, T cells were transferred to a large-scale cell expansion system, where they continued to grow for an additional five days.

Total cell number and cell viability before bioreactor transfer (day seven) and after harvesting (day 12) were found to be statistically indistinguishable between robotic and manual versions of this culture process. In both conditions, cell yields were greater than live cells and viability remained above 95%.

To ensure the maintenance of cell quality, gene expression analyses were performed, and no statistical differences were observed in differentiation, exhaustion, and proliferation markers between the manual and robotic conditions. In fact, only 0.45% of approximately 28,000 genes analyzed were differentially expressed between the two conditions.

In addition to cell count and viability successes, none of the robotic cell expansion samples were contaminated. However, one of the three manual T-cell expansions was positive to S. epidermidis, which is found on human skin and supports the conclusion that removing human hands from manufacturing processes can help prevent microbial contamination.

“In summary, the prototype robotic cluster demonstrated comparable cell yields, viability, and identity when compared to manually cultured cells,” explained Parietti. “This is a critical finding for the scalability and availability of cell therapies, given approximately half of cell therapy manufacturing costs are driven by labor and limitations on skilled labor. The high cost of personnel coupled with necessary facility and equipment expenses have contributed to the extremely high prices for cell therapy and therefore limited patient access.”

While robotics and automation are common approaches to reducing labor costs in other industries, it is more challenging in biomanufacturing changing instruments or processes in FDA-approved therapeutics manufacturing requires regulatory resubmissions and comparability studies. Multiply Labs decided to address this issue by focusing on robotic systems that can operate GMP instruments from multiple different vendors, which are already deployed for cell and gene therapy manufacturing.

The company’s strategy enables plug-and-play-like capabilities, and fewer regulatory barriers, as no major process changes are required for robotic compatibility, maintains Parietti, adding that while this proof of concept focused on cell expansion, there is promise in applying the same approach to cover the whole end-to-end cell therapy manufacturing process by automating more instruments in a similar way.