Flexible Cell Processing Platform Enabling Redesign of a CAR-T Manufacturing Process

Case Study: Flexible Cell Processing Platform Enabling Redesign of a CAR-T Manufacturing Process

MilliporeSigma take us through integrating the ekko platform into a second generation manufacturing process
Situation

A developer of a CAR-T therapy has recently completed IND enabling studies on its product and is beginning to build a clinical data set demonstrating its safety and early efficacy against an unmet indication. However, as the therapeutic developer looks to the future and mulls over its entry into phase II and III trials, an analysis of the manufacturing process currently used raises a number of red flags around process robustness and the subsequent impacts on its ability to meet stricter acceptance criteria for lot release moving forward.
 
As the therapy developer approaches this intersection in its lifecycle, process development projects are undertaken to redesign and improve this manufacturing process.
 
 
Challenge

A review of the manufacturing process finds a range of process technologies in use across the unit operations. Some steps, notably material preparation for electroporation, also require manual processing, which introduces risks around variance and contamination. Higher level challenges also exist in the difficulty of integrating of the manufacturing steps into an overall process, for instance the weight sensor requirements of the harvest equipment preventing direct connection to the expansion vessel.
 
 
Solution
After contacting the MilliporeSigma cell therapy processing team, PD scientists at the therapy developer were provided a technical questionnaire and performed a detailed review session with MilliporeSigma field applications specialists to ensure process needs were correctly understood. Using these outputs an evaluation program was developed alongside the customer that assessed the ekko Acoustic Cell Processing system as a multifunctional piece of equipment able to perform multiple unit operations across the manufacturing process. The three areas of interest during such an evaluation were:
 
  1. the wash of incoming thawed apheresis material
  2. concentration and wash in of buffer prior to gene modification with an electroporation system
  3. and the harvest of cells following expansion. 
Exemplar data sets of ekko performance during each process can be seen below.
Exemplar data sets of ekko performance during each process can be seen above.

As well as performing data generation activities around each unit operation, field application specialists at the equipment provider worked with process development scientists at the therapeutic site to determine the best methods for integrating the ekko platform into the manufacturing process with sterile connections to upstream and downstream equipment and helping to ensure that the second generation manufacturing process will greatly reduce risk, remove complexity, and improve consistency.
 
Working together, the therapy provider and supplier were able to successfully redesign and simplify the CAR-T manufacturing process by using one piece of equipment for three unit operations.  

About the author
 
Benjamin Ross-Johnsrud, Technology Expert, Cell Therapy Processing, MilliporeSigma
Benjamin Ross-Johnsrud, Technology Expert, Cell Therapy Processing, MilliporeSigma


Ben Ross-Johnsrud is a Technology Expert for Cell Therapy Processing at MilliporeSigma and came to the team through the recent acquisition of FloDesign Sonics, Inc. As part of his role, Ben leads customer engagement activities, demonstrating the capabilities of our acoustic cell processing technology, the ekko™. He is an expert in conceptualizing new manufacturing paradigms, using the full breadth of the acoustic technology and MiiliporeSigma cell therapy product portfolio to create solutions that meet the adapting process requirements and growing needs of commercial cell therapy supply.