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From Left: Dr Liu Dan, Ahmad Amirul bin Abdul Rahim

 

Science

Automation is key to reducing manufacturing costs and consequentially improving the accessibility of the highly promising cell and gene therapies. However, current cell and gene therapy manufacturing faces challenges due to variability in patient cells and inconsistent product quality. To address this challenge, regular analysis of the cell and culture quality during manufacturing is essential. The development of DAAS addresses this need by enabling automated, small-volume (0.02 to 1.00 mL) sterile sampling from cell manufacturing systems with minimal culture loss for regular cell analysis.

 

Societal Impact

DAAS is developed to address the specific sampling requirements during cell and gene therapy manufacturing. It helps streamline manufacturing process, reduce manpower requirement, and minimise the use of high-grade cleanroom, saving manufacturing costs and making the therapies more affordable and accessible. It can potentially be paired with other automated systems to perform in-line cell analysis and in-process adaptive control during cell culture, helping progress the cell therapy manufacturing process towards a higher degree of automation.

 

Technical Summary

DAAS is an automated, functionally closed system that enables automated small-volume (0.02 to 1.00 mL) aseptic sampling with minimal dead volume for cell and gene therapy manufacturing. It consists of a single-use disposable unit, which is replaced for every new manufacturing run, and a functional unit, which serves as a capital device across the runs. It performs aseptic sampling by drawing the entire culture into DAAS, followed by separating the target sample volume at an aseptic barrier along the flow path. The target sample volume is then dispensed either to an open collection well or sterile sampling pouch for cell analysis. The culture preceding the aseptic barrier is then returned to the cell culture system with minimal dead volume.

Repeated microbial ingression testing with E.Coli was performed to verify DAAS’s aseptic sampling capability. A comparison with manual technique using pipette was also conducted using cell solutions comprising of Jurkat cells of different concentrations demonstrating that DAAS can perform comparably to the manual technique, with negligible sample carryover between repeated sampling events. The capability of DAAS to perform regular sampling for analysis without detrimental effects on cell was then validated in a 10-day experiment using Jurkat cell culture.

Figure 1. Integration of DAAS into a fully automated cell and gene therapy manufacturing workflow, where regular sampling for analysis potentially enables close cell culture monitoring and prompt in-process adaptive control.

 

References

Dan L, Ying Ying W, Prabhu AV, bin Abdul Rahim AA and Jia Sheng ZL (2024) Device for automated aseptic sampling: Automated sampling solution for future cell and gene manufacturing. Front. Bioeng. Biotechnol. 12:1452674. doi: 10.3389/fbioe.2024.1452674