High Throughput vs. High Precision: Which CLD Strategy Works for You

• icon-date-svg April 3, 2025
• icon-time-svg 10:33 am

High-Throughput vs. High-Precision: Which CLD Strategy Works for You?

What is High-Throughput Cell Line Development?

High-throughput CLDenables the rapid generation of many potential clones within a single workflow. This method is especially useful in early discovery research, where scientists often study the effects of genetic variants or knockdowns on a specific phenotype. Some experimental strategies introduce multiple genetic modifications into a single cell pool, followed by cell sorting to assess the effects of individual changes on clonal populations. For example, CRISPR technology has been used for genome-scale gene knockouts in CHO cells, helping to identify clones with enhanced ability to produce "challenging" proteins (Shin et al., 2025).

In such cases, researchers' primary focus may lean towards ensuring the genetic alteration has been successfully implemented rather than clonality of the population. Although confirming true clonality remains important for research accuracy, the need to rigorously demonstrate clonality is less strict than it is when developing a cell line for therapeutic use.

While these approaches are fast and yield many clones, they can involve compromises in clonality verification, which can impact scientific rigor and the reliability of downstream data. Even in early discovery, where standards are less strict than for therapeutic CLD, failing to achieve clonality can make conclusions unreliable, potentially requiring researchers to repeat the entire screening process.

What is Precision Cell Cloning?

By contrast to high-throughput CLD, precision cell cloningprioritizes clonality verification, long-term performance, and compliance with regulatory requirements. Precision cell cloninghelps to generate cells using a process that complies with requirements needed to produce biologics, such as the production of monoclonal antibodies or cell-based therapies (European Medicines Agency (EMA), 1998). These requirements are in place to safeguard product quality, consistency, and end-user safety. Researchers who fail to present robust evidence of clonality risk regulatory rejection, delays in development, and increased costs (FDA', 1997).

To achieve regulator-ready precision cell cloning, development teams can leverage modern technological advances. This includes systems that capture images of single cells during dispensing, as well as imaging on the growth surface to track their expansion over time. Researchers can further safeguard CLD processes by screening cells for desired characteristics such as high production of target proteins (Yang et al., 2022).

Advanced instrumentation and software, such as the UP.SIGHTand C.STUDIO from CYTENAhelp researchers capture and manage large volumes of data. This technology makes it simple for researchers to generate clonality reports, which streamlines regulatory submissions (Fig. 1).

Without modern technologies, researchers performing CLD risk significant time loss and reagent waste, as traditional methods like limiting dilution introduce the risk of human error and contamination (Coller & Coller, 1986).

Application Scenarios: Which Strategy Fits Your Workflow?

Both high-throughput CLDand precision cell cloningare valuable single-cell dispensing techniques, each best suited to specific applications and stages of development.

• Biotech Discovery Stage: A higher throughput approach is optimal to begin with, allowing researchers to screen cell populations for desirable traits without spending unnecessary effort or resources focusing on stringently achieving clonality. This approach can be followed up by more precise regulatory-focused cell cloning once lead populations are identified.
  
  
• CDMOs: The goal is to produce high-performance clones that clients can take forward for regulatory approval. With this in mind, researchers should focus on precision, generating the necessary documentation to support applications.
  
  
• Cell Therapy and Gene Editing: Precision is mandatory when performing CLD for these therapeutic applications. The risk of heterogeneity threatens regulatory approvals and end-user safety.
  
  

A crucial parameter in CLD is knowing which cell line best suits your application. Visit CYTENA's biopharma cell line databaseto identify tried and tested cell lines for drug and protein production applications.

Choosing a CLD Path

Choosing the best approach can be challenging for researchers, especially smaller teams, as it's crucial to use limited time and resources as efficiently as possible. Time spent ensuring clonality can be time wasted when performing broader screening. Conversely, "faster" approaches may lead to long regulatory delays if they come at the expense of precision. The costs of failed drug development ranges in the hundreds of millions (per drug), making early strategic decisions pivotal (Sertkaya et al., 2024).

Choosing the right approach is important, but teams often need to balance high throughput and precision throughout different development stages. Fortunately, a solution is available that enables researchers to benefit from speed and precision.

CYTENA's instrumentsprovide a unified system for CLD, supporting any application by combining high-throughput processing with guaranteed clonality in a single workflow. This means researchers don't have to compromise on speed or precision when approaching discovery or regulatory-ready submissions.

The UP.SIGHT instrumentensures >99.99% probability of clonal derivation, which helps researchers achieve high throughput with less starting material. Combined with the C.STUDIOand F.QUANT assay for measuring antibody titer, this instrument offers precision with high throughput for advanced uncompromising CLD processes that generate regulatory-ready documentation with CFR Part 11 compliance.

Conclusion: Tailoring Strategy to Science

There's no one-size-fits-all approach to CLD, but with the right tools, researchers don't have to choose between speed and precision. Whether you're screening thousands of clones in early discovery or generating regulatory-ready cell lines for therapeutic use, CYTENA's platforms let teams adapt their workflows as needed. With automation that supports both, your team can accelerate development without compromising on data quality or regulatory compliance for cell lines.

Contact a CYTENA expert todayor read our product comparison page to identify the solution that best fits your CLD workflow.

References

oller, H. A., & Coller, B. S. (1986). Poisson statistical analysis of repetitive subcloning by the limiting dilution technique as a way of assessing hybridoma monoclonality. In Methods in Enzymology (Vol. 121, pp. 412-417). Elsevier.

ICH Q5D Derivation and characterisation of cell substrates used for production of biotechnological/biological products-Scientific guideline | European Medicines Agency (EMA). (1998, March 31).

ich-q5d-derivation-characterisation-cell-substrates-used-production-biotechnological-biological-products-scientific-guideline

Points to consider in the manufacture and testing of monoclonal antibody products for human use (1997). U.S. Food and Drug Administration Center for Biologics Evaluation and Research. (1997). Journal of Immunotherapy (Hagerstown, Md.: 1997), 20(3), 214-243.

Sertkaya, A., Beleche, T., Jessup, A., & Sommers, B. D. (2024). Costs of Drug Development and Research and Development Intensity in the US, 2000-2018. JAMA Network Open, 7(6), e2415445.

Shin, S. W., Kim, S. H., Gasselin, A., Lee, G. M., & Lee, J. S. (2025). Comprehensive genome-scale CRISPR knockout screening of CHO cells. Scientific Data, 12(1), 71.

Yang, W., Zhang, J., Xiao, Y., Li, W., & Wang, T. (2022). Screening Strategies for High-Yield Chinese Hamster Ovary Cell Clones. Frontiers in Bioengineering and Biotechnology, 10, 858478.