Advances in cell line development

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Reece Armstrong offers an overview of cell line development and outlines the benefits the technology is bringing to biopharmaceutical developers.

Cell line development is an essential underpinning of the drug development process, enabling teams to test, optimise and manufacture therapeutics at a commercial scale. It is a crucial for the development of biopharmaceuticals since they use a living host to produce the therapeutic in question. 

The market for cell line development is currently rising due to an increased focus by the life sciences sector on biopharmaceuticals and targeted therapies. According to Grand View Research, the global cell line development market was valued at $4.81 billion in 2022, a figure that is expected to grow at a compound annual growth rate (CAGR) of 9.81% from 2023 to 20301.

Grand View Research states that the market for cell lines is currently bolstered by the fact that the majority of biopharma companies use cell lines to synthesise recombinant monoclonal antibodies and proteins. One of the most recent drivers of the cell line development market came from the Covid-19 pandemic, where research into vaccines skyrocketed and demand for cell lines was boosted as a result. 

For drug discovery and development, cell lines allow researchers to test the efficacy of therapeutics before moving into in vivo studies. It’s an essential step in determining whether a therapy is effective and can help reduce the cost and time it takes when bringing a drug to market by enabling researchers to submit investigational new drug (IND) or a biologics license application (BLA) to the Food and Drug Administration (FDA). 

Commonly used cell lines include CHO (Chinese hamster ovary) cells and HEK 293 (human embryonic kidney 293) cells. CHO cells are typically used for the large-scale production of monoclonal antibodies (mAbs) and recombinant proteins since their ability to grow and divide rapidly under controlled bioreactor conditions makes them suitable for higher yields when producing therapeutics proteins. HEK 293 cells on the other hand are used within viral vector productions which have wide-scale applications for vaccines and therapies. 

There are a lot of considerations to take when choosing a cell line. For instance, bacteria and yeast cell lines are easier to cultivate compared with mammalian cell lines, requiring less maintenance for the medium they are grown in. Their faster growth means that teams could reach an IND filing quicker but there are other considerations to make as well. For instance, mammalian cells are better at providing characteristics that are similar to human physiological conditions. Mammalian cell lines also offer other advantages when compared with bacterial cell cultures, such as producing biologics, conducting disease assays, enabling studies into cellular functions, and evaluating drug efficacy and toxicity more accurately. 

Moreso, CHO lines are well established within the industry and platforms are currently supported by a range of tools that can increase productivity and quality. The fact the technology is recognised by the FDA means that approvals could be garnered more quickly if teams are using well established cell line development platforms.

Bacterial cell lines such as E. coli have their own set of benefits however. Bacterial cultures can grow extremely healthy and can withstand more drastic temperatures undertaken during the transfection method – which allows plasmid DNA to enter bacterial cells. Mammalian cell lines on the other hand can suffer damage during this process which can affect how the cells then replicate1.

E. coli cell lines are also able to easily develop certain proteins such cytosolic and excreted proteins but are not easily able to express membrane bound proteins, making them less useful for studying mammalian proteins. 

Looking towards the future 

Technological advances are helping drive efficiencies in cell line development. Cell culture techniques have traditionally been done using manual methods that are incredibly laborious. Automation has emerged as a tool which teams now use to free-up the time scientists spend doing manual tasks for cell lines and also to ensure the consistency of cell cultures and reduce the chances of contamination2.

Automation can be a pivotal tool in the process of colony screening – a method that’s undertaken after transfection where a large number of clonal cells are screened and selected based on how well they express the protein of interest. Automation enables teams to screen hundreds of thousands of clones, outpacing traditional workflows and ensuring stability and product quality3.

Cell culturing has traditionally been conducted in 2D environments such as petri dishes. This type of 2D biology has a wealth of literature for teams to fall back on but ultimately doesn’t represent how cells actually operate and interact with each other within the body. 

As such, 3D biology like organoids and spheroids that are grown in a scaffold or matrix can better mimic the conditions of an in vivo environment, giving teams more physiologically relevant information for cell line development. However, as a comparatively young technology, 3D cell cultures can remain inconsistent between organisations since there isn’t a standardised way to grow them. 

Recent years have also seen the development of technologies that enable a better genomic and transcriptomic analysis of single cells. For cell lines, this means that teams have a greater understanding of cellular heterogeneity and are able to optimise cell culture conditions and select clones with the characteristics they require, improving the overall development of cell lines4.

Looking ahead, it’s clear that the role of technology is playing a big role in advancing cell lines. With the pharmaceutical sector increasingly focused on targeted treatments such as antibodies, developers will be more dependent on cell lines. As such, if they can utilise technologies to enhance productivity and increase the quality of cell lines, the path to market will be easier and less burdensome for biopharmaceutical developers.

DDW Volume 25 – Issue 2, Spring 2024

References

  1. https://www.caltagmedsystems.co.uk/information/bacterial-vs-mammalian-expression-systems/
  2. https://www.researchgate.net/publication/245472064_A_Review_of_Cell_Culture_Automation 
  3. https://www.moleculardevices.com/lab-notes/clone-screening/challenges-of-cell-line-development-and-emerging-technologies-to-regulate-monoclonality#challenges-of-a-traditional-cell-line-development-workflow 
  4. https://lifesciences.danaher.com/us/en/library/biotechnological-impact-cell-line-development.html

Reece ArmstrongAbout the author

REECE ARMSTRONG is Editor of DDW. He has worked in life sciences and pharmaceutical B2B publishing for seven years and was previously Editor of European Pharmaceutical Manufacturer. He has a master’s degree in Journalism from Newcastle University.

 

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