Thu. Nov 30th, 2023

Contract development and manufacturing organizations are increasingly important to pharmaceutical companies. CDMOs work as partners in bringing biologic drugs to market and manufacturing them at scale, and biologics are one of the fastest expanding segments of the pharmaceutical industry. These biologic drugs begin with cell line development, the process of culturing cells in the lab to produce therapeutic proteins and antibodies.

Cell line development has its roots in the early 20th century. Plant and bacteria cells can be used, but Chinese hamster ovary (CHO) cells, first isolated in the late 1950s, have become the workhorse of the biopharmaceutical industry. These CHO cells can create glycans, a key ingredient in monoclonal antibody production, and they can fold and create large proteins that non-mammalian cells are unable to produce.

Advances in molecular biology techniques, such as gene cloning and transfection methods, have further refined the process. The field has continued to advance with the introduction of new technologies and methods, such as the use of the gene-editing tool CRISPR and high-throughput screening, which have made it possible to create cell lines with specific characteristics more efficiently.

Today, cell lines are a critical component in the biologic drug development process, and they’re integral to the work of CDMOs.

“These are exciting times for the cell line development (CLD) market. An ever-increasing need for biologics to treat oncological, autoimmune, and infectious diseases is leading companies to seek more efficient and effective CLD support,” writes Youlim Kim, a lead scientist in CDMO Samsung Biologics’ cell line development group, in a recent piece for The Medicine Maker.

“This growing demand for biologics — primarily bispecific and [monoclonal antibodies], recombinant proteins, and vaccines — has fueled remarkable growth in the CLD market, which is currently enjoying a double digit growth compound annual growth rate (CAGR) and is predicted to hit $1.7 billion by 2028.”

How Cell Line Development Works

While it involves culturing and altering living cells, cell line development is an in vitro process, which means it’s conducted without the use of a living organism. Parental cell lines developed decades ago can be carried on and altered in lab settings.

Cell line development in a lab involves a few key steps. First, scientists pick a suitable type of cell, usually a CHO cell. Next, they insert a special piece of DNA into these cells so they can produce a specific protein or antibody. Developers then select the cells most efficient in making the protein or antibody and test them to make sure they’re stable and of high quality. Once they find the best cells, they grow them in larger quantities while making sure they continue to meet quality standards.

Cells are typically grown in bioreactors that mimic natural conditions for cell reproduction. This involves using a nutrient-rich liquid called a culture medium, which provides essential elements like amino acids, vitamins, and minerals that cells need for growth and function.

Bioreactors can range from small flasks to large industrial vessels and are equipped with features like stirrers for even nutrient distribution and sensors to monitor conditions like pH and oxygen levels.

Best Practices

Strategic planning and early assessment of viability are keys to developing quality cell lines, says Kim.

“Having good CLD processes in place early can help you keep sight of your larger [investigational new drug] or Biologic Licence Application goals. And by considering all aspects of the product lifecycle from the outset, you’re setting yourself up for commercial success down the road.”

The choice of an initial cell line is crucial, and cell lines that come with a robust set of preexisting data can streamline timelines by reducing the need to gather data.

To meet dual objectives for quality and efficiency, CDMOs have to fine-tune the conditions under which cells are cultured, employ cutting-edge technologies for cell screening, and tailor cell lines to the specific needs of the project using data-driven decision-making.

In some cases, CDMOs will work with external collaborators that offer tailored solutions for cell culture mediums, which is particularly useful for molecules that are challenging to produce in high quantities.

Kim also points out the importance of using tools capable of handling large volumes of samples, which along with analytical methods and machine learning, can markedly speed up workflow.

One way to overcome bottlenecks is through the application of high-throughput analytic methods. These methods allow for the rapid collection of data, which can then be used for informed decision-making.

“Fail fast, fail early” is a guiding maxim, because early analysis and developability assessments will direct focus on molecules with the highest probability of success at the beginning stages, thereby reducing risk and improving confidence as a project progresses.

By Manali