Cells deliver myriad functions that make our existence possible. The activity of cells underlies all basic functions of an organism, but most of us never think twice about it. Yet, those who study cells at a molecular level know there are many secrets to their processes that could save human lives, some of which science is just beginning to unlock. Among the most promising: the potential to turn cells into living factories, churning out revolutionary drugs to combat ailments that have plagued humanity for centuries. This idea is at the heart of a rapidly advancing field known as cell line development. The future of medicine is being rewritten, one cell at a time.

“Efforts to pioneer therapies for incurable diseases, the expiration of branded drugs, and the emergence of new afflictions are factors driving growing demand for cell line development,” writes Daniel Buckley, lead scientist in cell line development at Samsung Biologics, in a recent white paper. “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.” 

Cell Line Development: An Overview

Cell line development is akin to crafting a unique and finely tuned assembly line, but instead of assembling car parts or electronics, the cell line is programmed to produce specific molecules essential for medicine.

A cell line is essentially a family of cells, all descendants of a single ancestor cell. These cells are grown in controlled conditions to ensure that they multiply while retaining their ability to accurately and repeatedly produce a specific molecule. The types of cells used can vary, ranging from insect cells to mammalian ones, with Chinese hamster ovary (CHO) cells being a particularly favored choice in the biopharmaceutical realm.

With the right tweaks and under the right conditions, these cells transform into prolific factories, working around the clock to produce molecules that can be harvested and turned into groundbreaking treatments.

Key characteristics for an effective cell line include: high productivity, stability, scalability, and safety. Cells need to produce the desired molecule at high levels. The cell line should be able to maintain its productivity over long periods and as demand grows, it’s crucial for the cell line to be reproduced on a larger scale without losing its qualities. Finally, the cells must not produce harmful byproducts or carry viruses that might contaminate the medicine.

How Cells Produce Medicines

Cells are like nature’s nano-factories, conducting a series of well-coordinated chemical reactions. In cell line development, scientists introduce specific genes into cells, turning them into specialized producers. This is akin to placing an order at a factory for a particular product. Once inside the cell, the gene acts as a blueprint, instructing the cell’s machinery to produce the desired protein or molecule.

The produced proteins are then harvested, purified, and formulated into medicines. It’s a transformative process where a tiny cell can yield lifesaving drugs.

A Glimpse Into the Future of Pharmaceuticals

Traditional pharmaceuticals, like the aspirin in your medicine cabinet, are small molecules made through chemical synthesis. In contrast, biopharmaceuticals are often larger, more complex molecules produced using living systems like cell lines.

The implications of this distinction are significant. Biopharmaceuticals can target distinct cellular pathways, offering treatments with potentially fewer side effects. These drugs can also be tailored for rare diseases that are difficult to target with traditional pharmaceuticals and thus are often deprioritized by drug makers. And, while it’s still an intensive and complex process, using biologic manufacturing grounded in a reliable cell line can lead to quicker drug development compared to conventional methods.

Case Study: Samsung Biologics’ S-CHOice

Contract development and manufacturing organizations (CDMOs) are leading the way in cell line development. One example is CDMO Samsung Biologics’ S-CHOice platform. 

This platform is a high-performing cell line development system based on CHO-K1 cells. What sets it apart is its glutamine synthetase knock-out system. This eliminates the GS gene to facilitate the selection of highly expressive cell clones. Samsung Biologics’ system has shown promising results in terms of efficiency and productivity. In practical terms, this means the platform can achieve improved titers, a measure of the concentration of the desired molecule, reaching above 7 g/L for standard monoclonal antibodies. Furthermore, according to Kim and Buckley, the cell line has demonstrated impressive viability, maintaining over 90% of its activity on the 21st day of a study.

The platform incorporates the Beacon system, which is designed for precise single-cell cloning, a process that identifies and isolates high-yield and high-quality cell lines. This system is fully automated, capable of screening 5,000 individual cells to pinpoint those that perform best. Such efficiency is crucial in the biotech industry, where the ability to quickly and accurately identify productive cell lines can significantly accelerate drug development timelines.

The challenges in cell line development are significant, but the opportunities are even greater, pointing toward a future with more effective and personalized health care, and quicker, more responsive drug production.