Cryopreservation

Corning X-WASH System: DMSO Reduction of Cryopreserved Human Mesenchymal Stem Cells

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Cryopreservation is a necessary part of workflows for both autologous and allogeneic therapies. The ability to cryopreserve cells for cell therapy increases the range of administration, shelf life, and time for safety testing. Cryoprotectants such as dimethyl sulphoxide (DMSO) often are added to freezing media to increase post-thaw cell survival. However, DMSO itself can be cytotoxic, so reducing its final concentration can be necessary. Below, I demonstrate how the Corning X-WASH system can reduce the amount of DMSO used in…

August 27, 2021

Freeze Cycle Testing of
Fluoropolymer Bottles

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Frozen storage of bulk drug substances (BDS), including bioprocess solutions, vaccines, blood components, and other delicate process fluids is common in the bioprocess industry. Vessels used to store those fluids must be capable of withstanding long-term storage in extremely cold temperatures (e.g., –85 °C or –196 °C), sometimes for very long time periods. They also must also maintain integrity after repeated thawing and subsequent refreeze. The study below was performed to characterize performance of fluoropolymer bottles with standard and two-piece…

August 27, 2021

Contractor Perspectives: Best Practices for Transfer, Handling, Testing, and Storage of Cell Banks

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For comments about how contract development and manufacturing organizations (CDMOs) manage their cell-banking quality assurance (QA) practices. I contacted long-time member of BPI’s Editorial Advisory Board Scott M. Wheelwright, PhD, for his perspectives. Wheelwright brings many years of experience to this discussion, with insights into the evolution of technologies and practices extending back to the early launch of the biopharmaceutical industry. Currently, he provides consulting support for companies with manufacturing and sourcing in China and other Asian countries. He also…

June 23, 2021

Single-Use Systems for Storing and Shipping Frozen Drug Materials

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Using presterilized, single-use freeze–thaw systems instead of traditional freeze–thaw platforms that include stainless-steel tanks and bottles can help biomanufacturers manage the quality of their drug substances. Single-use assemblies reduce the risk of cross-contamination, simplify dispensing, and decrease the number of manual interventions during freezing, thawing, handling, and shipping. However, implementing a freeze–thaw process requires careful testing of the physical and thermal properties of single-use systems and related aseptic connectors as well as assessment of drug-substance quality and stability. Such evaluation…

June 1, 2021

Cryopreserved Leukapheresis Materials Help Alleviate Donor Sourcing Issues

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Reliable access to high-quality starting material is a primary challenge in cell therapy manufacturing. Freshly isolated leukopak starting materials depend on donor availability and are vulnerable to cell losses from scheduling changes and other unforeseen circumstances. Flexibility often is required for cell therapy manufacturing. Therefore, relying solely on freshly isolated starting material is impractical, particularly when cell therapy logistics involve global shipping and distribution. Donor sourcing is among the most critical factors shaping cell and gene therapy (CGT) supply chains.…

December 6, 2020

Ask the Expert: Key Considerations for Cryogenic Preservation and T-Cell Viability

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Cryopreservation provides critical protection for cell therapies by minimizing genetic changes. But cooling too slowly or quickly risks diminishing cell viability upon thaw. On 11 March 2020, Peter Kilbride (senior research scientist) and Julie Meneghel (cryobiologist), both of Cytiva (formerly GE Healthcare Life Sciences), discussed the importance of controlled-rate cryopreservation. Illustrating how mammalian cells change when frozen, Kilbride and Meneghel offered concrete cryopreservation strategies and identified temperatures at which it is safe to stop controlled cooling and transfer drug product…

May 24, 2020

Cell Banking for Cell and Gene Therapy: Regulatory, Ethical, and Scientific Considerations

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Regenerative medicine holds great potential for human disease management, with hundreds of cell and gene therapy (CGT) products for tissue/organ reconstitution or replacement in different stages of development and clinical testing for toxicity, safety, and efficacy. For example, currently more than 60 CGTs have marketing authorization (although many with only conditional approval) from central regulatory agencies worldwide (1). Those products are treating conditions such as hematopoietic malignancies, immunological disorders, and cartilage disorders. Most of those treatments use culture-expanded autologous or…

January 31, 2020

The Critical Role of Media in Intensified Upstream Processes

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As the need for novel therapeutics increases, so does pressure on the biopharmaceutical industry to improve productivity, accelerate development, increase, and reduce costs — all while ensuring drug product quality. Upstream intensification strategies such as perfusion culture can address those challenges and achieve higher protein titers that can translate into higher throughput, improved flexibility, and compressed timelines. Successful implementation of perfusion culture or the transition to perfusion from fed-batch culture requires a different and strategic approach to media selection, not…

October 28, 2019

Development of Large-Scale Bulk Freezing Systems

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The biopharmaceutical industry is under pressure to generate value for shareholders and find innovative therapies while driving down development and manufacturing costs. As the industry considers more flexible and scalable production solutions for patients, new therapies will continue to be developed faster than ever before. These products will need to rely on robust and reliable manufacturing solutions. To deliver on that challenge, streamlining manufacturing processes will be necessary so that many lots of drug substances can be manufactured, stored, and/or…

February 14, 2019

A Novel 3D Culture System for High-Throughput Hepatoxicity Screening

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Cells grown as three-dimensional (3D) spheroids are thought to more closely mimic in vivo physiology in terms of morphology, structural complexity, and phenotype. Being more physiologically relevant, 3D cultures can be highly predictive for compound profiling and evaluating cytotoxicity, a critical step in evaluating chemotherapeutic drug candidates. Unfortunately, evaluation of drug cytotoxicity traditionally has relied on the use of two-dimensional (2D) cell culture monolayers. When grown in monolayers, cells are not exposed to soluble gradients, are forced into an apical-basal…

October 20, 2018