Cryopreservation is the process of using ultra-low temperatures to preserve living cells for long periods of time. It is an essential aspect of the cell manufacturing process of many cell therapies. While there are multiple factors to consider for developing a cryopreservation process that will ensure safe and effective manufacturing of cell therapies, below are four of the most important ones.
Controlling the Rate of Freezing is Essential to Preserving Therapeutic Value
Patient cells that have been harvested and processed for therapeutic use, will be cryopreserved and shipped to the patient where they will be thawed and transplanted. The cryopreservation process must be done carefully to maintain cell integrity and therapeutic value.
Fundamental to successful storage is the preservation of the cells while preventing damage. Cryoprotectants, such as dimethyl sulfoxide (DMSO), which infuse into the cells during the freezing process, help prevent cell damage. The cryopreservation process must be performed at a specific cooling rate, usually 1°C/minute, until the sample reaches -50°C in order to preserve the sample’s integrity during the freezing cycle. Once the sample reaches -50°C it can be quickly brought to the final storage temperature of -196°C for long term storage. Controlled rate freezing before storage maximizes viability for a wide variety of cells.
Selection of the Right Cryopreservation Vessel
In general, it is critical to select a system that is closed, scalable and adheres to Good Manufacturing Practices (GMP) for cryopreservation. Cells are often cryopreserved in vials, as they are easy to handle and can be used to establish seed banks for large-scale allogeneic (donor-derived) cell therapy production. However, for autologous (patient-derived) cell therapies, such as some CAR T-cell therapies, vials are not the best choice. The amount needed for a final patient dose may exceed billions of cells and will most likely not be able to fit in vials. Additionally, vials are not suitable for administering the cell dose to patients at the clinical site.
An alternative solution would be to cryopreserve cells in a freezing bag designed for cryogenic storage of cells. The variety of sizes available allow for the storage of greater numbers of cells, which provides greater flexibility. The use of cryogenic bags is not without its own challenges, however, as these bags don’t offer an automated solution. The key takeaway is to select a system that can accommodate a wide range of patient dosing volumes to ensure the best outcomes for cell storage.
Traceability Throughout the Cold Chain
The cold chain for a medical product is the sequence of transportation events required to maintain temperature within approved specifications from the manufacturer to the end user. Cold chains are used for the distribution of pharmaceuticals and biologic products, and have been used for decades. For cell therapy products, this presents the unique challenge of maintaining living cells in a viable state from storage to distribution.
In other words, it’s necessary to ensure a safe and effective cold chain to keep cells in the best possible condition until it’s time for them to be administered to a patient via cell therapy.
Additionally, whether the cells are allogeneic (donor-derived) or autologous (patient-derived), measures must also be taken to ensure the security and traceability of cells from extraction to administration. It should be routine to trace a cell sample from tissue isolation to patient delivery, with enough security to maintain patient confidentiality. The traceability of cells throughout the cold chain not only ensures that patient information remains confidential, but also ensures the safety and quality of the cells from their manufacture all the way through to their use in cell and gene therapy.
Automation for Closed-System Workflow
There are many benefits to automated cell banking for cell manufacturing, including making processes more time and cost efficient. Saving time and money not only makes life-saving cell therapies, such as CART-cell therapy, more affordable for patients, but also increases their availability for more people around the world.
Closed system workflows help minimize contamination risks.
These are systems designed to operate in a way that doesn’t expose the cells to the room environment, and their use increases the safety and efficacy of the cell manufacturing process.
An automated system like the BioArchive® uses proven computer-controlled technology and tracking software, which offers the best protection for cell samples collected today and ensures their viability when it’s time for their use.
How ThermoGenesis Can Help
The BioArchive® System offers cell storage, tracking, and retrieval with automation and certainty. The system offers constant temperature control through closed-system sample handling with robotic storage and retrieval, resulting in minimal exposure to transient warming events (TWE). These are brief exposures of cryopreserved products to temperatures above the critical (ideal for cryopreservation) temperature. This highly innovative product automates the cryopreservation process and boasts a 94 percent post-thaw cell viability rate. The Sample Management Software (SMS) provides accurate, individualized, fully documented freeze and sample tracking, history and inventory, ensuring GMP-compliance.
ThermoGenesis Holdings, Inc. is a pioneer and market leader in the development and commercialization of automated cell processing technologies for the cell and gene therapy fields. We market a full suite of solutions for automated clinical biobanking, point-of-care applications and large-scale cell processing and manufacturing with a special emphasis on the emerging CAR-T immunotherapy market. We are committed to making the world a healthier place by creating innovative solutions for those in need.
For more information on our entire suite of automated solutions, please contact our sales team.