Cell Therapy Development

Cell therapy process development is nearly impossible with current tools. With expensive, scarce, and variable donor/patient cells having a scale down model that provides enough useful data can be difficult. Erbi Biosystems is looks to provide cell therapy therapeutics developers a platform to build a more robust and understood manufacturing process by carrying out more process development experiments, in less time, at a smaller volume and with fewer hours in the lab.

Cell Therapy Customer Dilemmas

ALL CELL THERAPY: The rush to the clinic reduces the amount of time/effort spent developing a manufacturing process. Every process will be unique for each therapeutic and requires significant optimization.  Regulators are delaying products due to CMC and developers have a narrow window while the PH1 trial is running to improve the process before PH2, especially if they get RMAT designation. Developers are time, people and hardware limited in carrying out these studies.

AUTOLOGOUS CELL THERAPY: Processes are developed using healthy donor apheresis units and much optimization is done in plates or flasks. Experiments done at closer to manufacturing scale (1L) are laborious, take up significant bench space and the number of technical replicates from a single donor is limited. These limitations decrease the experimental throughput, which limits the design space that can be investigated. Once a process is developed, testing the manufacturing process on patient material who have the relevant indication is hard to do since obtaining the apheresis is nearly impossible. Testing patient to patient and within patient variability is difficult and hard to control.

ALLOGENEIC CELL THERAPY: Stem cells must be expanded and then differentiated into a specific cell type.  Expanding the stem cells requires constant monitoring of the cells and feeding with media that contains a complex mix of growth factors and supplements. Development of a differentiation process requires the addition of different growth factors at different times throughout the differentiation process which can range from 10 to 60 days.  DoE-style experiments are needed to develop an optimized differentiation process and these studies are often done in 6 well dishes, which do not allow for the same level of control and feeding seen in STRs. DoE at larger scales require higher numbers of input stem cells and the media costs can quickly become prohibitive as the media + supplements could be more than $1k/L and the protocol could call for daily media exchanges

How can the Erbi Breez help?

MORE EXPERIMENTS: The ease of use, reduced footprint, and low volume requirements of the Erbi reactors allows customers to carry out more experiments by more efficiently using the developers most limited resources: scientists, bench space, and precious reagents.

LESS TIME: Testing more conditions in parallel allows customers to test more conditions at once, reducing the total number of experiments required to characterize a manufacturing process.

LOW VOLUME: A closed, controlled, and perfusion-enabled 2mL bioreactor allows customers to build a manufacturing process that can be tested on patient derived cells and generate high numbers of replicates to fully understand the variability of the manufacturing process.

Demonstrated CT Performance 

Cell therapy process development is nearly impossible with current tools. With expensive, scarce, and variable donor/patient cells having a scale down model that provides enough useful data can be difficult. Erbi Biosystems is looks to provide cell therapy therapeutics developers a platform to build a more robust and understood manufacturing process by carrying out more process development experiments, in less time, at a smaller volume and with fewer hours in the lab.

 

Example 1: High density T cell culture 

  • Greater than 180M cells/mL
  • 100X expansion
  • Ratio of CD4/CD8 was maintained within 1% of replicates
  • Reproducible quality maintained

Visible Cell Density

Fold Expansion

Data representative of actual customer results

Example 2: Examine donor reproducibility through growth and phenotype in different media systems

  • Multiple replicates using single done source
  • Multiple runs with varying media, supplements
    • Proves media optimization worthwhile
  • Tight process repeatability across multiple runs
  • High correlation to baseline
  • T-cell expansion to densities of 100M/mL
  • MORE Experiments in LESS Time with FEWER Resources

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