Enhancing cell line development and streamlining processes
Single-cell technologies are removing barriers and boosting productivity within complex cell line development processes to transform the delivery of novel biotherapeutic molecules for contract development and manufacturing organisations (CDMOs) such as FUJIFILM Diosynth Biotechnologies.
CDMOs provide critical support services for pharmaceutical and biopharmaceutical companies working in highly competitive environments, aiming to deliver the most robust and efficient cell lines that demonstrate the best possible productivity. But this can be challenging due to the shift in focus in the field of biological medicines, away from conventional therapeutic monoclonal antibodies towards antibody fragments and bispecific antibodies that are more difficult to express in cellular systems. This is a fast-paced area of the drug development industry, and timelines for cell line provision are under increasing scrutiny as companies compete for their share of the marketplace.
To complicate matters further, evidence of monoclonality proving that the cell line producing the therapeutic molecule is derived from a single parent cell is required to obtain approval from industry regulators such as the Food and Drug Administration (FDA). Companies must prove that the cell line producing the therapeutic molecule is derived from a single parent cell. Time-consuming and low-throughput conventional screening techniques, such as colony picking and limiting dilution cloning, do not allow individual cells to be visualised, and monoclonality can be difficult to demonstrate using these methods. Higher throughput screening technologies, such as fluorescence-activated cell sorting (FACS), provide a more efficient approach, but they can be complex to use, are only able to detect membrane-bound antibody and may risk damaging delicate cell lines as suspensions are driven through the system under pressure.
Using Sphere Fluidics’ Cyto-Mine technology, FUJIFILM Diosynth Biotechnologies has implemented a new single-step cloning technique, bypassing the traditionally time-consuming, multistep selection, isolation and verification process. Researchers are now able to swiftly transition from the initial transfection phase through to the delivery of highly productive research cell banks within timelines of approximately 10 weeks. Following this approach, pools of transfected cells are encapsulated as single cells within individual picolitre-sized aqueous droplets in a biocompatible carrier oil (picodroplets). Each picodroplet provides a defined and supportive environment that maintains cellular viability. Single cells and their secreted proteins are rapidly screened and characterised within a fully automated, high-throughput workflow.
Previously, screening required lengthy manual procedures and analysis techniques. As its assays are miniaturised within a single, integrated platform, Cyto-Mine allows analysis that may once have taken weeks to finish to be completed within one day. Approximately 200,000 cells can be screened in a matter of hours, compared with around 10,000 cells with multistep manual techniques that run over a number of weeks. Using this streamlined approach, researchers have been able to identify highly productive recombinant cell lines within significantly shorter timelines. Crucially, single cells can be visualised using the Cyto-Mine system, providing evidence of monoclonality and helping to meet regulatory requirements.
Leveraging Cyto-Mine, workflows are considerably more efficient as cellular screening is conducted early in the process, allowing the best-performing cells expressing the protein of interest to be selected and taken forward for development. This offers benefits regarding the use of resources, including reduced reagent requirements and optimised laboratory space due to the incorporation of multiple screening, sorting and validation steps within one machine. The user-friendly approach also provides greater freedom from laborious manual procedures for scientists working in the laboratory, allowing them to apply their skills and expertise to other essential aspects of their work.
In a rapidly expanding and competitive marketplace, biopharmaceutical companies are seeking to combine quality with capacity. Technologies like Cyto-Mine, which enable greater productivity while supporting quality improvements, represent an attractive proposition to meet the needs of biopharmaceutical development companies and satisfy the requirements of regulatory bodies. In applying these enhancements, biologics development processes are streamlined and less labour-intensive, revolutionising timelines for the development of groundbreaking new medicines to prioritise speed to clinic.
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