Abstract
Cell therapies are increasingly recognized as advanced treatments for conditions like cancer and diabetes, through the introduction of healthy, viable cells into patients. These therapies utilize various cell types, including iPSCs, MSCs, engineered immunotherapies, and exosomes, each offering unique benefits. One key challenge throughout scaling up (increasing production volume) and scaling out (expanding production capacity) is the cell harvest as well as associated recovery of highly viable cells in a closed, automated manner. In certain separation methods, such as filtration, the harvest and recovery stage can be a challenge due to the risk of losing cells either to filter surface or from shear across filter membranes. The following case studies highlight the use of single-use tubular bowl centrifugation as a scalable and automated solution for varying cell lines while maintaining high viability and achieving high cell recoveries.
Methodology and Results
Empirical studies were conducted to assess the scalability of the following single-use tubular bowl centrifuges at varying processing volumes with push-button automated recipes:
- UFMicro® – Small Scale Process Development (<3L)
- UFMini® – Process Development to Small Pilot (3-20L)
- UniFuge® Pilot – Pilot Scale to Manufacturing (>20L)
Three case studies were reviewed to evaluate the effectiveness of scalability between the UniFuge systems, or a combination of the three. Critical process parameters of the centrifugation equipment, such as separation feed flow rate, relative centrifugation force, processing volumes, and cell types, were compared for cell recovery and cell viability changes from one machine to another.
1- Induced Pluripotent Stem Cells (IPSC) with scaled harvest volumes of 5L to 20L between the UFMini and UniFuge Pilot centrifuges yielded >95% recovery with a 1% difference in viability.
2- Autologous Primary Cells expanded and harvested as single cells scaled from 1L to 3L between the UFMicro and UFMini centrifuges yielded 100% recovery with an estimated 2% loss in viability.
3- Chinese Hamster Ovary (CHO) Cells with scaled harvest volumes from 500mL to 1L to 20L from the UFMicro to UFMini to UniFuge Pilot yielded >95% cell recovery with a maximum viability change of 5%.
The results from the studies demonstrate the ability of the UFMicro, UFMini, and UniFuge Pilot to maintain consistent performance such as cell recovery exceeding 95% and viability changes less than 1%, enabling manufacturers to scale processes confidently while maintaining a closed and automated system. Achieving consistent results across process development, pilot, manufacturing, and commercialization scales with varying cell types is crucial for the successful implementation and commercialization of cell therapies, ensuring both efficacy and safety for patients.
Conclusion
Single-use tubular bowl centrifugation delivered consistent, reliable, and scalable results across varying cell type, processing volumes, and scale. As scalable results become increasingly critical from early-stage process development to manufacturing, maintaining critical quality attributes, such as viable cell recovery and washing efficiency, without manual manipulation, is essential. This low-shear separation method ensures cell health and overall quality during scale-up and scale-out processes, which provide biomanufacturers confidence as they navigate different phases of clinical trials and associated approvals.
About Harvest Technology
The UniFuge line of Single-Use, Tubular Bowl Centrifuges by CARR Biosystems, is comprised of the UFMicro, UFMini, UniFuge Pilot, and U2k®, which enable automated, scalable solutions for cell and gene therapy manufacturers, as well as other separations and harvest applications in bioprocessing. The UniFuge line provides consistent results whether recovering cells or clarifying supernatants.
