In recent months we have provided in depth coverage on new CHO cell culture technologies, media supplements and manufacturing equipment. CHO related topics continue to be highly searched at The Cell Culture Dish. In light of its popularity, we wanted to provide a brief overview of the use of CHO cells for manufacturing and a review of our cell culture coverage that includes new technologies, best practices and key cell culture recommendations.
According to a report late last year issued by PhRMA, there are over 900 biotech drugs in development in the United States and many of these will be manufactured using CHO cell culture. As these drugs move from research to commercial applications, a host cell line is chosen to take the drug into large-scale commercial manufacturing. CHO cell culture is a popular choice.
When evaluating possible host cell lines for these drugs, several factors need to be considered. Primarily the technology has to work, i.e. it has to be able to correctly produce folded proteins that have the proper posttranslational modification. They also have to easily be genetically modified and have the capacity for high expression levels. Lastly the cell lines have to be safe and not susceptible to adventitious agents. Through years of using CHO cells in the lab for many types of studies, it was confirmed that they met many of these requirements.
CHO cells had been used for many years in laboratory work beginning in 1919 for typing pneumococci. Their use declined after domestication problems led to hereditary diseases due to imbreeding. Then in 1957, Dr. Theodore T. Puck from the University of Colorado’s Department of Medicine first established ovary cells in culture plates and found that they had good viability and grew rapidly. In light of this new research, CHO cells began being used in many types of lab studies, which ultimately led to their selection as a host cell line for recombinant proteins. According to Jayapal, Wlaschin, Yap, and Hu (2007) nearly 70% of all recombinant protein therapeutic productions is done in CHO and sales for biologics produced in CHO is over $30 billion worldwide.
The first product produced in CHO cells, approved in 1987, was a recombinant therapeutic protein manufactured by Genentech called Activase. Early biopharmaceutical manufacturing using CHO cells was much different than production today. Early manufacturing runs were conducted as batches and ran for 7 days with yields around 100 mg/liter and the media in which the cells grew contained animal products, such as fetal bovine or fetal calf serum. When bioreactors were introduced run times moved to 10-14 days with media and nutrients being replenished during the run. Now commercial biopharmaceutical manufacturing utilizes bioreactors 10,000 – 25,000 liters and larger in size. Media and nutrients for the cells are monitored continuously as well as oxygen levels, CO2 levels, and waste product. This constant information about cell health has led to more efficient and productive culture with average production yields from 1-6 grams/liter.
The manufacturing process has undergone continual improvements since commercial production began. Cell line development, media formulation and improved manufacturing equipment have become critical to successful, high yield production. These topics have been covered in the Cell Culture Dish blogs listed below.
Recent Blogs that Address CHO Cell Culture:
- How Single Use Systems are Improving Bioprocess Development
- The Impact of the Cell Culture Process on Product Quality
- Employing Perfusion Bioreactors to Improve Antibody Production in CHO Cells
- Strategies for Enhancing Media to Improve Antibody Production in CHO Cells
- Utilizing Gene Synthesis to Improve Antibody Production in CHO Cells
- Strategies for Improving Antibody Production in CHO Cells
- Mammalian Cell Alternatives to CHO Biomanufacturing
- CHO Cells – The Top Expression System of Best Selling Biologic Drugs
For further reading see:
- Jayapal K. P., Wlaschin K. F., Yap M. G. S., & Hu W-S. (2007). Recombinant protein therapeutics from CHO cells — 20 years and counting. Chem. Eng. Prog.,103(7), 40–47.