Cryopreservation: A Key Element in the Successful Delivery of GMP Cell Therapies
The Importance of Cryopreservation in GMP Cell Therapy
Cryopreservation is a process that preserves cells and tissues by freezing samples to very low temperatures over a period of time. It’s important to the cell therapy manufacturing process because cell samples need to be properly stored in order to maintain their viability and functionality later down the road when they’re thawed for use in patient treatment.
The treatments that are considered to be most safe and efficient are the ones that were manufactured under Good Manufacturing Practice (GMP) standards. These are guidelines published by health authorities to regulate every step of the manufacturing and production process of a drug, from product development and selection of raw materials to storage and shipment prior to use in patients. In order to meet these guidelines and provide the best possible therapies to patients, it’s essential to carefully execute the cryopreservation process.
The Cryopreservation Process
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 process. 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. Equally important to controlling the rate of freezing is the maintenance of the cells in the final storage temperature. Avoiding any fluctuations in temperature by exposure of the cells to the ambient environment is critical to maintaining cell viability and functionality.
Protecting Cryopreserved Cell Samples
The cryopreservation process also utilizes the addition of a cryoprotectant, a chemical component of a freezing solution, to minimize damage to the cells that can occur during the cryopreservation process and long-term storage. The cryoprotectant, most commonly dimethyl sulfoxide (DMSO), helps to protect the cells from freeze damage, and maintains the cell quality, extending its shelf-life. The freezing of cells can bring about a number of cell injuries, which can lead to changes in characteristics and damage that reduces the viability of the cells, rendering them less effective when they’re thawed.
Selecting The Right Cryopreservation Vessel
The selection of the appropriate storage vessel is another important consideration for cell 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, vials are not “closed” to the immediate environment and therefore must be processed in a biological safety cabinet as great care must be taken to prevent contamination. For autologous (patient-derived) cell therapies, such as some CAR-T cell therapies,the amount of cells needed for the 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 cell dose to patients at the clinical site.
An alternative solution would be to cryopreserve cells in a freezing bag designed as part of a “closed” processing system for cryogenic storage of cells. The freezing bag ensures there is no exposure to the surrounding environment, preventing ingress of microbes. The variety of sizes available allow for the storage of greater numbers of cells, which provides greater flexibility. Cryofreezing bags are also compatible with administration to patients in the clinic.
Automated Cell Manufacturing and Storage Solutions with the BioArchive System
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 us.
