1 April 2024 TechBio company, Cytomos (www.cytomos.com) was featured in the Genetic Engineering & Biotechnology News insights section.
The true long-term potential of complex therapeutics, such as monoclonal antibodies and advanced therapy medicinal products, will be unlocked only by the deployment of the next-generation technologies that are being developed to overcome current challenges—including challenges in cell cytometry. Ultimately, through improvements in process monitoring and control, flow cytometry will facilitate smart biomanufacturing.
The state we’re in
Since the first flow cytometers became commercially available around half a century ago, the technology has become mainstream across several disciplines. In summary, flow cytometry is based on a beam of light (usually a laser) directed at cells flowing in a stream of fluid. Labels such as fluorescent chemicals are applied to emit specific light signals, the scatterings of which are detected and analyzed. In this way, flow cytometry provides selected quantifiable data from cells.
Common applications, depending on the labels used, include cell counting and sorting, biomarker detection, cancer diagnosis, microorganism or protein detection, and determining predefined cell characteristics. In biomanufacturing, flow cytometry can be incorporated into cell sorters that physically separate and purify cells of interest based on their optical properties.
However, flow cytometry has limitations. For example, variations in sample preparation performed by different operators can lead to bias, whereas the need for labels (which necessitates the predefinition of parameters for detection) can reduce the scope of analysis. And if flow cytometry data isn’t “digestible,” the need for frequent complex downstream analyses can arise, potentially delaying the data-driven assessments that lead to informed decisions. Such limitations can prevent flow cytometry from being a suitable tool for quick and unbiased decision making.
Vision quest
It is generally expected that over the next 5–10 years, alternative process analytical technologies and next-generation cell analysis technologies will become sufficiently developed to enable greatly enhanced online and offline information gathering. Moreover, these technologies will probably be used alongside conventional flow cytometry.
In particular, advanced process analytical technologies are anticipated to serve as key drivers for accelerating new product discovery, development, and manufacturing. Cutting-edge techniques combining technology and biotechnology—TechBio—may hold the key to unlocking the true long-term potential of complex therapeutics such as monoclonal antibodies and advanced therapy medicinal products. This is due to their ability to radically decrease the cost of bringing products to market while becoming more robust and reliable through process insight and understanding. It is expected that TechBio will enable the industry to finally address the demand that manual processes transition to automated operations, a key goal in manufacturing.
To make that vision a reality, several challenges need to be overcome. The following challenges are among the most important:
• Unbiased, digestible data: Data must be unbiased, without the need for complex downstream analysis, allowing for earlier, better informed, and more consistent decisions.
• Label-free analyses: Eliminating the need for markers and reagents can enhance the scope of cell analysis, streamlining sampling and monitoring. For example, generating multidimensional profiles of individual cells without having to predetermine detection parameters makes it possible to detect a broader scope of features—inside and outside the cell—simultaneously for real-time analysis. It also makes it possible to go back and reevaluate the data with a different hypothesis and still derive value from it, due to the unbiased measurement.
• Real time: Real-time data collection and analysis enables at-line, in-line, and on-line applications for real-time monitoring, ultimately opening up the potential for automation and control. This necessitates a digital infrastructure capable of supporting the collection, management, and interpretation of a larger number of data points.
• Improved control: Better live monitoring of cell populations would help operators foresee cell growth and type, enabling better control of differentiation protocols. For example, improving cell and gene therapy process control could expedite predictions of failure or success and enable signals for optimal harvest times. A good example could be quick and easy detection of T-cell exhaustion during manufacturing of immunotherapies.
• Stability and productivity: Cell lines need to be differentiated according to how stable and productive they are likely to be. Identifying suitable stability and productivity metrics could, for example, improve the development of CHO cell lines or HEK cell lines.
• Scalability and versatility: Technologies should be scalable and versatile so that they can be used in a range of form factors without changing the essence of the data—from benchtop instruments (in R&D and process development) to probe instruments (for bioreactors or other cell culture devices) to manufacturing systems.
A revolution is coming
Overcoming these challenges would revolutionize cell analytics and empower it to transform the life sciences. Streamlining cell line development by consistently and reliably identifying lead clones could help predict high-producing, stable cell lines and detect changes in cell phenotypes earlier in the process, bringing cost savings and superior outcomes in less time. This will require the development, adoption, and deployment of TechBio tools that obtain a multitude of data on the intrinsic properties of cells in real time.
Work that is ongoing at a number of organizations from academia, government, and industry (including Cytomos) will accelerate new product discovery, development, and manufacturing. Enabling technologies that overcome many of the limitations of current processes will advance and improve the engineering and manufacturing of complex therapeutics. Ultimately, processes that can be monitored in real time and tools that collect sufficient meaningful data will enable adaptive process control and deployment of automation, delivering on the promise of smart biomanufacturing.
To quote Robert F. Kennedy (1925–1968), “A revolution is coming … whether we will it or not. We can affect its character; we cannot alter its inevitability.” New TechBio tools in development today are going to revolutionize biotechnology from development to manufacturing. By better predicting success rates and reducing costs of cell and gene therapy development, these technologies have the potential to positively impact medical care for patients worldwide. Used correctly, they could help us achieve the goal of providing better access to safe and affordable medicines and vaccines for all, delivering life-changing advanced therapies to the world.
Fernanda Masri, PhD, is chief commercial and innovation officer at Cytomos.
01 April 2024
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