Cell line development involves culturing cells instrumental in the production of therapeutic proteins, antibodies, and other biopharmaceuticals. The right CLD strategy can make a huge difference for contract development and manufacturing organizations working to improve development timelines.
These CDMOs partner with drug makers to produce biopharmaceuticals at a variety of scales, and having an efficient, reliable cell line is crucial. While a handful of foundational cell lines have been around for decades, CDMOs and drug developers work to edit these cells in the lab, essentially turning them into living microscopic factories to produce the needed therapeutic ingredients in a pure form and at high volumes.
Experts at Samsung Biologics, the world’s largest CDMO by capacity, point out that maximizing efficiency in cell line development early in the drug development process is the key to a successful partnership.
“CLD timelines, product quality, and drug stability continue to impose difficult bottlenecks, but those hurdles can be overcome through the early-stage development and application of high-throughput analytic methods,” according to science experts at Samsung Biologics in a recent white paper.
“The data gleaned can be used to make informed decisions and to optimize resources, resulting in a more efficient and successful CLD process. Often, a CDMO partner is able to drive this effort forward, drawing from previous experiences.”
Background and Technological Improvements
Scientists began to utilize in vitro cell line development as early as the 1950s, cultivating cells in the lab for biomedical research. They used these initial cell lines to help develop a polio vaccine, study the effects of x-ray radiation on human cells, and for cancer research.
However, it wasn’t until the 1970s that the advent of recombinant DNA technology propelled this field into a new era. Recombinant proteins are produced by inserting a desired gene (often human) into a host cell’s DNA. The chosen cell lines then express the gene, producing the desired protein. Cell line development involves fine-tuning the cellular environment and manipulating genetic elements to optimize the expression levels of recombinant proteins, ensuring high yields necessary for commercial viability.
Following the advent of recombinant protein production techniques, advances in molecular biology and genetic engineering further refined the cell line development process, allowing for enhanced control over cell line characteristics. The most important recent technological advancements involve automation and high-throughput screening, which enables developers to evaluate a much larger volume of cells at an accelerated rate. This has led to faster selection of high-producing cell lines and has significantly reduced development timelines.
“Samsung Biologics uses high-throughput methodologies, exposing each molecule to different stresses commonly encountered during process or storage. The analytical results from this developability assessment are evaluated as a whole and then compared against the wealth of internal data within Samsung Biologics and/or against marketed products,” according to the whitepaper.
“Applying this platform early in development can completely negate the need to undertake cell line replacement by developing a commercial-quality line from day one.”
S-CHOice®: A Cell Line Development Case Study
Samsung Biologics cell line development platform is based on Chinese hamster ovary (CHO) cells, an industry standard for biologic development. Initially cultivated for research purposes in the 1950s, CHOs quickly garnered attention due to their ease of genetic manipulation and adaptability to various growth conditions. Their genetic stability ensures consistent protein production, which is pivotal in drug development. Additionally, their amenability to genetic engineering facilitates the insertion of human genes to produce therapeutic proteins.
Over the decades, an extensive understanding of CHO cell biology has simplified regulatory compliance, which is vital for accelerated drug development. These cells have the ability to perform human-like post-translational modifications, have scalability for industrial production, and have a track record of regulatory acceptance.
S-CHOice® platform is Samsung Biologics’ CHO cell line development platform. It leverages a high-performing CHO-K1-based cell line built on glutamine synthase knock-out technology. The elimination of the glutamine synthase enzyme in CHO cells enhances cell viability and maximizes titers, a critical measure of the concentration of a product within a solution.
The goal is to accelerate timelines by identifying high-quality candidates early in the development process using high-throughput screening, then optimize titer with the CHO-K1 technology. This ultimately saves time by ensuring that cell lines won’t have to be revised further down the line when other aspects of the development process have already been put in place.
“To use a common industry maxim, it is better to ‘fail fast, fail early’ than to pour massive investment into a molecule that is not developable. This way, organizations can focus personnel, resources, and capital on the molecules with the highest probability of success — reducing risk and improving confidence in the molecule,” the whitepaper discusses.
“Toward this end, some companies now execute elements of process characterization earlier than they used to, attempting to facilitate a more seamless commercial launch, because the data generated at a very early stage has increased their confidence to do so.
“For this reason, CDMO partners are likely to become even more critical to the biopharma industry, enabling greater successes than the industry has seen to date.”