What Cell Lines Are Commonly Used in Biopharmaceutical Production?
Biopharmaceuticals, including recombinant proteins, monoclonal antibodies, and gene therapies, have revolutionized the treatment of a wide range of diseases, from cancer and autoimmune disorders to rare genetic conditions. The production of these complex, biologically-derived molecules relies heavily on the use of specialized cell lines, which serve as the workhorses of the biomanufacturing process. These diverse expression systems, carefully engineered and optimized, enable the efficient and consistent production of biopharmaceutical compounds, meeting the ever-increasing demands of the global healthcare market.
Expression Systems Used in Biopharmaceutical Production
The selection of an appropriate cell line is a crucial decision in the development of any biopharmaceutical product. There is a comprehensive portfolio of mammalian, microbial, and insect cell lines, each with its unique capabilities and advantages.
| Expression systems | Bacterial expression systems | Yeast expression systems | Mammalian cell expression systems | Insect cell expression systems |
| Examples | Escherichia coli | Saccharomyces cerevisiae, Pichia pastoris | Chinese hamster ovary (CHO) cells, Human embryonic kidney (HEK) cells | Spodoptera frugiperda (Sf9) cells |
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| Applications | Production of recombinant proteins, enzymes, and insulin. | Production of vaccines, hormones, and enzymes. | Production of monoclonal antibodies, therapeutic proteins, and viral vaccines. | Production of vaccines, therapeutic proteins, and virus-like particles. |
Types of Cell Lines Used in Biopharmaceutical Production
Biopharmaceutical production relies on various cell lines to produce therapeutic proteins, vaccines, and other biologics. Each cell line has unique characteristics that make it suitable for specific applications. The following are some of the most commonly used cell lines in biopharmaceutical production.
CHO cells
CHO cells are renowned for their ability to perform complex post-translational modifications, which are essential for the proper folding and biological activity of many human therapeutic proteins. CHO cells are commonly used for the production of monoclonal antibodies, recombinant proteins, and other biopharmaceuticals.
HEK 293 cells
HEK 293 cell line is derived from human embryonic kidney cells, which are capable of performing human-like post-translational modifications, making them a suitable choice for the production of viral vectors, recombinant proteins, and other biologics. HEK 293 cells have gained regulatory acceptance for certain human therapeutic applications.
Baby hamster kidney (BHK) cells
BHK cell line, derived from the Syrian hamster kidney, is also a widely used expression system in the biopharmaceutical industry. BHK cells are capable of performing complex post-translational modifications and are often employed for the production of various viral vaccines and recombinant proteins.
Sf9 cells
For insect-based expression systems, the Sf9 cell line, derived from the fall armyworm, is a popular choice. Sf9 cells are capable of performing many post-translational modifications and are utilized for the production of recombinant proteins, virus-like particles, and viral vectors.
Vero cells
The Vero cell line, derived from the kidney of the African green monkey, is primarily used for the production of viral vaccines, such as those for polio, rabies, and COVID-19. Vero cells have gained regulatory acceptance for some human therapeutic applications.
NS0 cells
The NS0 cell line, a mouse myeloma cell line, is commonly used for the production of monoclonal antibodies and other recombinant proteins. NS0 cells can perform complex post-translational modifications, making them a suitable choice for biopharmaceutical manufacturing.
Madin-darby canine kidney (MDCK) cells
The MDCK cell line, derived from the kidney of a Cocker Spaniel dog, is utilized for the production of influenza vaccines and other viral vaccines. MDCK cells have also gained regulatory acceptance for certain human therapeutic applications.
Cell Line Characteristics and Requirements
Regardless of the specific cell line employed, several key characteristics and requirements must be met to ensure successful biopharmaceutical production.
- Firstly, the cell line must exhibit robust growth characteristics, including the ability to thrive in suspension or adherent culture formats, as well as the capacity to reach high cell densities in bioreactor systems. This is essential for achieving the necessary volumetric productivity to meet the demands of large-scale manufacturing.
- Secondly, the cell line must demonstrate consistent and reliable protein expression, ensuring the production of biopharmaceutical compounds with the desired quality attributes, such as proper folding, glycosylation, and biological activity. Genetic stability and the maintenance of the desired phenotype over extended culture periods are also critical parameters.
- Additionally, the cell line must be capable of performing the necessary post-translational modifications required for the proper function of the biopharmaceutical product. This is particularly important for mammalian cell lines, which are adept at replicating the complex modifications found in human-derived proteins.
Regulatory Considerations
The use of cell lines in biopharmaceutical production is subject to stringent regulatory guidelines and requirements to ensure the safety, efficacy, and consistency of the final products. Regulatory bodies, such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), have established comprehensive guidelines for the characterization and validation of cell lines used in the development and manufacturing of biopharmaceuticals.
Maintaining consistency and reproducibility in cell line-based biopharmaceutical production is of paramount importance to ensure the quality, safety, and efficacy of the final products. Regulatory authorities require robust and well-controlled manufacturing processes to minimize variability and ensure product quality.
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| Cell Line Authentication | Creative Bioarray offers an accurate and reliable method for authentication of cells and cell lines, which is a STR analysis service. |
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Reference
- Dumont J, et al. (2016). "Human cell lines for biopharmaceutical manufacturing: history, status, and future perspectives." Crit Rev Biotechnol. 36 (6): 1110-1122.
