In a previous Cell Culture Dish blog, titled “Chinese Hamster Ovary (CHO) Cells – the Workhorse Behind Many Biotech Drugs,” I outlined the history and importance of CHO cells as a way to manufacture biologic drugs at commercial scale. I was recently reminded of just how important CHO cells are to biopharmaceutical manufacturing, particularly the best selling biologics. According to Huggett, Hodgson and Lähteenmäki (2011) the top five selling biologic drugs in 2010 were Enbrel, Humira, Remicade, Avastin and Rituxin. Of these top sellers, four out of the five are manufactured using CHO cells, all with annual revenues over six billion.
|Rank||Biologic||Expression System||Company||2010 Worldwide Sales in Millions||Approved Indication|
|1||Enbrel||CHO||Amgen||6,808||RA. ankylosing spondylitis, psoriasis, PA, juvenile rheumatoid arthritis|
|2||Humira||CHO||Abbott||6,548||RA. ankylosing spondylitis, juvenile rheumatoid arthritis, Crohn’s disease, PA. psoriasis|
|3||Remicade||Murine Myeloma||Johnson & Johnson||6,478||Psoriasis, ulcerative Myeloma colitis, ankylosing spondylitis, Crohn’s disease. PA. RA|
|4||Avastin||CHO||Roche||6,193||Colorectal cancer, breast cancer, brain cancer, renal cell cancer, non·small cell lung cancer|
|5||Rituxin||CHO||Biogen-Idec||6,088||Non·Hodgkin’s lymphoma, RA, chronic lymphocytic leukemia|
We have come a long way since Genentech’s Activase, the first product produced in CHO cells, was approved in 1987, but that technology was critical in laying the foundation for the kind of biologic manufacturing that exists today. CHO cells had good viability, grew rapidly, were easy to culture and had the ability to reach high expression levels, all of these factors made them an excellent choice as a “manufacturing” cell line. Of course, early biopharmaceutical manufacturing using CHO cells was much different than production today. The first 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. Then bioreactors began to be used and 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.
These improvements were critical to CHO’s long-term success and have kept them as a top choice in manufacturing since the early 1990’s. How long will CHO cells remain the workhorse for the biopharmaceutical industry and are further improvements possible to improve cost and reduce capital investment? Can cell culture changes, media improvements or cell culture supplements get us where we need to go or have we reached the peak of CHO performance?
Please comment on what technologies are out there to push CHO cells to higher performance and cement their place in the future of biologic drug manufacturing?