What is Cell and Gene Therapy?
Cell therapy and gene therapy are technically two separate treatments that are closely related and sometimes overlap as they both fall under the umbrella of “precision medicine.” Precision medicines are tailored treatments based on each patient’s genes or other unique characteristics. When a disease is caused by mutations in a person’s genes, gene therapy typically utilizes viruses (which are altered to not cause any disease symptoms) to deliver a “healthy” version of the gene into a patient’s body. In cell therapy, damaged cells are replaced or repaired by transplanting human cells into the patient.
As scientists continue to develop new breakthroughs to treat diseases, cell therapy and gene therapy are combined into cell and gene therapy, or cell-based gene therapy, as it may also be called. In this treatment, cells are removed from a patient to be altered using gene therapy and later implanted back into the patient’s body to fight disease.
Cell and gene therapy has a history going back decades, with a wide range of technologies and clinical trials tested since 1980, including gene-editing techniques. One well-known technique, called CRISPR/Cas9, was developed to modify specific DNA sequences in 2012 and would have its first clinical trial initiated in 2018. CRISPR, or clustered regularly interspaced short palindromic repeats, uses a specially designed RNA molecule to guide a Cas9 enzyme to a specific sequence of DNA to change or edit that site sequence.
In 2017, the FDA approved CAR T-cell therapy for the treatment of relapsed/refractory large B-cell lymphoma, which was later approved by the EMA in 2019. T-cells are part of the immune system and are developed from stem cells in bone marrow, so CAR T-cell therapy treatments, such as CARVYKTI, utilize a person’s T-cells that have been genetically modified to recognize and attack cancer cells.
Cell and Gene Therapy Logistics
As new cell and gene therapy (CGT) treatments continue to be developed, the unique logistics requirements of the supply chain are a major factor in the planning of clinical trials and other patient care. CGT is dependent on the living cells taken directly from a patient, and patient samples and finished CGTs have a fresh shelf life of only 12 to 96 hours. Through cryopreservation, which freezes cells in liquid nitrogen between -150°C and -196°C at the point where all biological activity is stopped, the CGT shelf life is extended and allows for longer-term storage.
Regardless of the temperature environment, it is crucial to ensure the best possible condition. Whether at controlled-room, refrigeration, ultra-low, or cryogenic temperatures, cell and gene therapy logistics present the following challenges:
- Strict regulatory compliance requirements
- Precise, validated temperature control
- Contingency planning to manage critical, time-sensitive transportation
- Data traceability, visibility, and management, including chain of identity and chain of custody
CGT manufacturers require a reliable cell and gene therapy logistics partner that adheres to stringent Current Good Manufacturing Practices (cGMP), validating processes, and can implement thorough Quality Assurance (QA) and Quality Control (QC) systems in addition to precision cold chain management, continuous monitoring, and comprehensive documentation to ensure sample safety and efficacy from the starting to the final destination.
Cell and Gene Therapy Storage
In the case of some cell and gene therapies, the process may be more complex and include multiple doses, therefore needing storage solutions as well as logistics. For example, CAR T-cell therapy involves two doses developed in a specialized manufacturing facility from a patient’s blood. The first dose is implanted back into the patient, and the second dose is typically held for long-term storage, though some clinical trials are now utilizing it to treat patients who had relapses, did not respond to the first dose, or extend initial remission.
Most cell and gene therapies are sensitive to changes in the environment and temperature. CAR T-cell therapy materials are often more volatile than other cell and gene therapies due to several factors, like high costs, complex and personalized manufacturing processes, and potential safety risks.
Due to their complexity and sensitivity, CAR T-cell second doses require ultra-cold (-135°C) or cryogenic storage to prevent degradation while maintaining viability. Even minor temperature fluctuations can impact dose efficacy and functionality, so consistent, stable temperatures are crucial to prevent cellular damage or degradation. To ensure temperature consistency, facilities storing CAR T-cell therapies must use extensive monitoring and alarm systems, reliable ultra-cold equipment with backup power systems, and contingency plans in case of equipment failure.
Cell and Gene Therapy Logistics and Storage Solutions
In 2017, following FDA approval, SciSafe signed a contract with our first partner in CAR T-cell storage, and since then, our logistics and storage solutions have evolved to include:
CAR-T Handling and Transport
Our trained technicians handle CAR T-cell products while maintaining cryogenic temperatures throughout transportation and storage. We utilize validated dry shippers to secure samples during transport with continuous temperature monitoring, and then the records are reported to the manufacturer upon receipt.
Comprehensive Logistics and Storage Support
SciSafe offers comprehensive logistics support, including IATA-compliant dock transfers, hand-delivered samples in liquid nitrogen, and 24/7 retrieval services. Our facilities provide 24/7/365 continuous monitoring, backup power systems, SOP-driven handling to maintain material integrity, and client traceability, along with business continuity and disaster recovery plans.
Accessioning and Inventory Management
Second dose CAR T-cell samples undergo rigorous accessioning processes, ensuring accurate documentation and digital storage of chain of custody and inventory manifests, as well as the secure management of any patient-specific information to comply with HIPAA protocols.
Quality Assurance and Compliance
In order to maintain stringent quality control measures in accordance with US FDA requirements, SciSafe offers triple sample inspections, temperature monitoring data and validation, and adherence to manufacturer-specific protocols. Plus, regular audits and documentation verification ensure regulatory compliance and high-quality storage standards.
If you would like to learn more about SciSafe’s precision cold chain logistics and secure storage solutions, contact us today. Or for more information, download SciSafe’s CAR-T Second Dose Storage Case Study.