Asian Scientist Magazine (Aug. 26, 2022) – In any process, an early awareness about the possible obstacles that could arise is key to making informed decisions and improving efficiency. This is especially true for developing cell lines, which are at the heart of scientific discovery and innovation.
Before biomedical interventions can make it to clinical practice, cell lines can be used to test the efficacy of a drug candidate against various diseases like cancer. As living environments, these cells can also serve as production centers for biopharmaceutical manufacturing by taking advantage of their complex metabolic machinery. For example, scientists can induce the cells to produce desired biomolecules such as recombinant proteins with therapeutic properties.
Evidently, stable and productive cell cultures are vital for biopharmaceutical production processes. However, cell line development is time-consuming and technically demanding, typically taking 12 to 18 months. Accordingly, biotech developers must recognize potential pitfalls and take preemptive measures to make the best possible decisions, from clone screening to cell culture expansion.
To address these challenges, scientists and innovators are exploring novel technologies to enable robust, high-yield and cost-effective cell line development throughout every stage of the pipeline.
At the earliest stage of cell line development, scientists are already faced with crucial decisions. The choice of cell line can make or break the entire process: the cells need to synthesize biomolecules with specific features and clinical functions—and do so in a sustained, highly productive way. When the cells are expanded to clonal populations, selecting a high-yield clone inevitably demands extensive screening and optimization.
Given that clonal performance is unpredictable, developers spend a long time screening numerous clones and perform several rounds of testing to look out for various indicators such as stability. Otherwise, they may end up wasting resources on expanding cell cultures that have suboptimal yield or that fail to capture the needed properties of the biological product.
To accelerate screening, iQue®, an advanced, high-throughput flow cytometry platform from Sartorius, can help scientists determine the likely best-performing clones. The platform calculates the viable cell concentration and paints a comprehensive picture of the molecular features of each clone. Such analysis is key to identifying the most productive clones and their required culture conditions. As a one-stop system, it also comes with the iQue Forecyt® Software, which enables interactive gating with real-time results.
Effective clonal selection also depends on examining critical quality attributes such as protein affinity and physicochemical characteristics. Instruments like the Octet® bio-layer interferometry system are key to this stage, enabling real-time and label-free analysis to guide selection of optimal clones. Later on, developers may also need to characterize the biologic products synthesized by the cells. To this end, Sartorius’ Octet® BLI technology can measure titer affinity and concentration up to 20 times faster than other techniques like high-performance liquid chromatography and ELISA.
By providing speedy analysis, these innovations in cell line technologies are helping reduce the rounds of optimization needed during screening. Developers can thus analyze cellular data with ease, choose the most desirable clone and take their projects to the next level.
Consistent cultivation and characterization
In building up a thriving cell culture, the environmental conditions and available nutrients play a significant role in influencing the cells’ growth rate and their capacity to produce the desired biomolecules. To provide optimal culture media conditions, developers can turn to bioreactor technologies such as Sartorius’ Ambr® platform. Through this integrated system, scientists can manage several experiments and cultivate several colonies simultaneously, improving the efficiency of the entire workflow. The bioreactor also serves as a controlled environment to enable a consistent performance and high yield.
During this stage, quality control mechanisms and thorough monitoring strategies are important for evaluating the cultured clones and the molecular products that they synthesize. For example, the product must be biocompatible, meaning that it can be safely introduced to the human body. Comparisons to a reference molecule may also be needed to ensure standardization, particularly when the product has been modified for a specific clinical function.
This diverse combination of functional and safety tests typically entails using multiple instruments and methods, which can be taxing on resources for smaller biotech companies. This challenge underscores the need for integrated analytic technologies to enable more efficient yet comprehensive characterization. Moreover, characterizing and documenting cell line features is vital for supporting future research and manufacturing endeavors, especially to ensure that regulatory standards have been met.
Consistency is key
What makes cell lines so powerful in the biopharmaceutical industry is the ability to continue producing new cells that retain the attributes of the ancestral clone. To maintain such integrity during cell line expansion, storage procedures and facilities are expected to comply with regulatory guidelines. Currently, the standard for cell line storage is through cryovial cell banking, where cells are frozen to preserve their biological characteristics. However, several barriers remain, such as contamination risks during manual banking as well as the differing conditions between lab-scale and commercial-scale manufacturing.
Compared to manual processing, cell line developers are recognizing the value of automated platforms like Sartorius’ Fill-It system to facilitate the rapid yet consistent production of high quality cell stocks. By ensuring that conditions remain consistent across large batches, such automated cell banking technologies help enhance the scalability of cell line development and downstream biologic production.
Purpose-built processing platforms
A scalable and sustainable supply of cell lines is key to continuously supporting scientific endeavors in the biopharmaceutical space. However, producing biologics is complex and the cell line development process is no exception. Scientists and process engineers face challenges with tight timelines, constant cost pressures and prolonged time-to-clinic.
But innovations in cell line development can address these issues by providing high-quality data on cellular characteristics and supporting better-informed decision-making. These purpose-built and integrated technological suites can help developers maximize efficiency while maintaining robustness at every stage of the pipeline. Ultimately, reliable and scalable cell line development paves the way for cutting-edge science—translating research into commercially viable and clinically impactful products.
With a three-pillar approach, Sartorius offers CLD customers the flexibility to select the technologies that are right for their therapeutic development.
To learn more about the challenges that plague cell line development and how manufacturers can better optimize bioprocessing, read Sartorius’ white paper on Accelerating Cell Line Development for Commercial Production here.
Illustration: Asian Scientist Magazine
This article does not necessarily reflect the views of AsianScientist or its staff.