Mammalian Cell Alternatives to CHO Biomanufacturing

Last week in a blog titled “CHO Cells – the Top Expression System for Best Selling Biologic Drugs” I discussed how CHO Cells are the manufacturing platform for four out of five top selling biologic drugs in 2010, each with annual revenues over six billion. At the end of the blog, I asked if there was a platform that could compete with CHO in biomanufacturing and this week, I thought I would highlight a few possible contenders.

Perhaps the biggest challenger to CHO cells right now is the NS0 cell line. NS0 cells are a mouse myeloma cell line and have demonstrated high protein expression similar to CHO cell production. However, some have raised issues related to glycosylation and in antibodies where glycosylation is a big factor, CHO cells may provide a closer to human glycosylation pattern. In addition some NS0 lines require extra supplements be added to media for highest titers. Supplements including lipids and cholesterols are required for some NS0 lines and this adds additional cost plus challenges to downstream purification.

Another cell line that has received attention is EB66, manufactured by Vivalis. EB66 is derived from duck embryonic stem cells. Vivalis states that these cells were created without any genetic, chemical or viral modifications and as such they have created a production system free of genetic instability or tumorigencity that can be found in other cell lines. They also claim that the glycosylation is more similar to human cells resulting in a more potent final product than what can be manufactured in CHO cells. One challenge of any proprietary cell line is that the licensee pays for use of the cell line, which over time can be costly and limiting.

One of the most talked about and most developed human cell lines is the proprietary PER.C6 cell line. The manufacturers of PER.C6, DSM and Crucell, have said that their cell line provides improved performance for biomanufacturing including some reports of titers up to 30 grams/Liter. They also provide completed safety documentation, pre-selected media and cell line optimization, saving time and resources. There are also advantages to using a human cell line in post-translational modification that results in a decrease in immunological reaction, an increase in pharmaceutical activity and improved pharmacokinetics in the final product. The downside is that royalties can be costly (some say double digit percentages) and ultimately media and manufacturing changes are less flexible and less accessible to in-house process development.

So how do these challengers stack up? I would like to know if any readers have compared these cell lines to CHO cells and if so do any have the potential to become the next biomanufacturing powerhouse? Is anyone aware of other cell lines that are better alternatives?