Optimizing Cryopreservation for Leukapheresis: Advancing Cell and Gene Therapy Supply Chains 

The supply chain for fresh leukapheresis is one of the most complex logistical challenges in cell and gene therapy (CGT). As a critical starting material, leukapheresis must be collected from donors, processed, and transported under stringent conditions, all within a limited time window. These challenges increase variability and risk, ultimately impacting the success of advanced therapies. To address these concerns, Alexandre Michaux, Process Development & MSAT Manager at IntegriCell™ , recently presented his work on the development of an automated cryopreservation process for leukapheresis in a Poster Presentation at Advanced Therapies Congress in London. This innovation aims to enhance consistency, scalability, and efficiency in CGT workflows. 

The Challenge of Fresh Leukapheresis in CGT Supply Chains 

Leukapheresis serves as the foundation for many cell and gene therapies, but managing its supply chain presents significant hurdles. Two primary challenges stand out: 

1. Limited Viability Window – Fresh leukapheresis has a short shelf life, meaning the cells must be processed and used quickly. Delays in logistics, donor scheduling, or manufacturing can compromise cell quality. 
2. High Variability – Since fresh cells are sensitive to time and environmental changes, inconsistencies in handling and transportation can introduce variations in product quality. 

Given these constraints, transitioning to a cryopreserved model offers a promising alternative. 

Why Cryopreservation? 

Cryopreservation stabilizes leukapheresis by freezing the cells in a controlled manner, preserving their viability and function for extended periods. This approach enables: 

• Greater Flexibility – Therapies can be scheduled based on manufacturing capacity rather than the immediate availability of fresh material. 
• Improved Standardization – A well-defined cryopreservation process reduces variability between samples. 
• Supply Chain Resilience – Transportation and storage become more manageable, reducing the impact of delays or unforeseen issues. 

However, effective cryopreservation requires precise optimization to maintain cell viability and functionality. 

Developing an Automated Cryopreservation Process 

Michaux’s team set out to design a cryopreservation process that is both automated and standardized, minimizing the risks associated with human handling and process inconsistencies, with the key goals to: 

• Reduce Variability – Ensure that every batch of cryopreserved leukapheresis meets the same quality standards. 
• Enhance Reproducibility – Develop a process that can be reliably implemented across different sites. 
• Maintain High Cell Viability – Optimize freezing protocols to preserve the integrity of the leukapheresis product. 

To achieve these goals, the team conducted a series of experiments comparing manual and automated cryopreservation approaches. 

Optimizing the Freezing Process 

The development process involved multiple parameters, including: 

1. Controlled-Rate Freezing – A precise cooling profile was established to prevent ice crystal formation, which can damage cells. 
2. Cryoprotectant Selection – The team optimized the concentration of cryoprotectants, ensuring they effectively protect cells without introducing toxicity. 
3. Automated Handling – By integrating automation, the process reduces operator-dependent variability, leading to more consistent results. 

The results demonstrated that the automated cryopreservation process significantly improved consistency and reproducibility while maintaining high cell viability. 

The Impact on CGT Manufacturing 

By shifting from fresh to cryopreserved leukapheresis, the industry can unlock multiple benefits: 

• Scalability – More efficient inventory management allows manufacturers to scale production without bottlenecks caused by donor scheduling. 
• Global Accessibility – Cryopreserved leukapheresis can be transported worldwide, expanding access to therapies beyond local donor networks. 
• Manufacturing Optimization – The ability to store cryopreserved leukapheresis material until needed enables better synchronization with production schedules.

Enabling the Future of Cell and Gene Therapy 

The development of an automated cryopreservation process for leukapheresis represents a major step forward in CGT supply chain optimization. By reducing variability, improving reproducibility, and enhancing supply chain flexibility, this approach has the potential to transform how advanced therapies are developed and delivered. 

With continued innovation in cryopreservation and logistics, the future of CGT looks increasingly scalable and reliable, which, in turn, ensures that life-saving therapies increasingly reach patients with greater efficiency and consistency.