Biologics are therapeutics developed using living cells, and they’re one of the fastest-growing sectors of the pharmaceutical industry. The European Pharmaceutical Review recently reported that biologics are set to surpass small molecules in sales revenue by $120 million as early as 2027. A key driver of this growth has been advancement in cell line development technology, which is enabling drug makers to produce the proteins and antibodies needed for biologics at higher qualities and with greater efficiency.
Another driver has been the rise of contract development and manufacturing organizations. CDMOs partner with pharmaceutical firms to develop and manufacture biologics. They act as contractors to produce drugs based on substances such as bispecific and monoclonal antibodies, proteins, and mRNA.
Cell line development is a complex process. It involves precise, strategic culturing and genetic alterations of living cells to produce the target molecules at scale without losing purity. While the technology has been around since the mid-20th century, it’s only in recent years that some of the pressing challenges in maintaining a stable, effective cell line for biopharmaceutical applications have been solved.
‘Technically and Operationally Challenging’
“Although the capabilities of biopharma’s contract development organization (CDO) partners are continually advancing, in the context of overall development, [cell line development] remains both technically and operationally challenging to accomplish,” according to a Drug Target Review article discussing why partnering with a competitive CDMO may help drug developers to expedite their development timeline while mitigating any chance of delays or erros to the lowest degree.
However, according to the article there are ways to overcome these challenges, including developing enhanced Chinese hamster ovary (CHO) cell lines and implementing high-throughput screening technology to identify viable cells at an early stage of drug development.
CHO Cell Line Development
CHO cell lines were first developed in the 1950s, and are now utilized in vitro. Developers don’t extract the cells from hamsters. Rather, they edit CHO cell lines that have existed for decades and can be grown and altered using genetic engineering and cell culturing.
“Reliable CHO cells lines are the ideal cell system to produce a variety of therapeutic proteins, including [monoclonal antibodies] and bispecific antibodies, and they have many advantages,” the article discussed.
These advantages include a relative ease of culturing compared to non-mammalian cells, protein folding capacity, high productivity, a similarity to human cells, and a track record of recognition and approval by regulatory bodies.
“There will be no viable product without correct protein folding, assembly, and [protein post-translational modifications] properly. Therefore, it is of utmost importance to use a cell line that is reliable and well characterized to avoid wasting time fixing issues that may arise from poor expression, folding, and assembly later in the process.”
High-throughput screening is a method that uses automated systems to quickly test thousands of different cell types under various conditions. The goal is to find the cells best at producing a specific protein or substance and to figure out the optimal environment for those cells to thrive. This rapid, automated testing helps researchers identify the most promising cells early in the cell line development process.
“Access to high-throughput tools, advanced analytical technologies, and current good manufacturing practice (cGMP) environments can rapidly accelerate [cell line development] programs,” the article explained.
“High-throughput technologies, such as affinity capture technologies, can be used to accelerate cell isolation, screening, and selection by making the process fully automated. Sorting using single-cell printing techniques and advanced artificial and machine learning automation could further increase the speed of production.”
Automation is particularly crucial, as it enables rapid data collection and minimizes human error. The technology can incorporate robotic systems, specialized software for data analysis, and advanced detection methods like fluorescence or luminescence assays.
The primary objective of using high-throughput screening in cell line development is to identify the cell lines that exhibit the highest yield, stability, and quality of the desired product. The screening process starts by transfecting a large number of host cells with a gene of interest. These transfected cells are then cultured under different conditions, such as varying nutrient concentrations or pH levels, to assess their performance.
Data generated from high-throughput screening is analyzed to determine key performance indicators like growth rate, protein expression levels, and metabolic stability. Advanced statistical methods and machine learning algorithms may be employed to interpret this large dataset, making it easier to identify optimal cell lines and culture conditions.
Promising New Treatments
Some of the most widely used therapeutics are now biologics, including the COVID-19 mRNA vaccines and drugs that treat conditions ranging from autoimmune disorders to cancer. This is in no small part due to advancements in cell line development technology.
The increasing demonstration of the effectiveness of these drugs is spurring investment in research, development, and manufacturing technology. CDMOs like Samsung Biologics, which just completed a fourth manufacturing plant and has a fifth in the works, have grown exponentially in recent years. Amid growing demand for biologics and increased outsourcing within the pharmaceutical industry, CDMOs are continuing to step up to improve cell line development processes.
“By working with a single, end-to-end CDMO partner, disconnects or operational gaps between the different stages can be limited or eliminated,” the article discussed. “Increasingly, the best-performing development programs come because of outsourcing [cell line development] to strong partners that fit the molecule best.”