Manufacturing Challenges of mAb Production: CHO or Plant Cells?

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The latest Ebola epidemic sheds light on the delicate processes surrounding the manufacture of genetically modified live cells for biopharmaceutical production.

Ramping up production of a biologic product in the event of a major health crisis can present major challenges for manufacturers and developers. Often, producing more therapies may not be as easy as simply recruiting more hands on deck, as live cells have to be grown over time, rather than chemically manufactured. Product quality can vary between batches within a plant, and therapies manufactured at various sites could also vary slightly in composition depending on host cell lines. Small variations in manufacturing processes can alter a medications safety or efficacy, impacting the reliability of the supply.

Despite these concerns, to properly address the growing threat of Ebola, regulatory authorities are joining together with drug manufacturers to investigate possible production solutions. The Biomedical Advanced Research and Development Authority has asked three centers how they can expand manufacturing of mAbs for ZMapp using tobacco plants. In a separate initiative, the Bill and Melinda Gates Foundation has given ZMapp’s maker Mapp Pharmaceutical Inc. a $150,000 grant to address large-scale production. Amgen has also offered its support to expand antibody production using Chinese hamster ovary (CHO) cells (1).

“Given the urgency to find a treatment for Ebola virus infection, Amgen will support the work of the Bill and Melinda Gates Foundation, along with the Wellcome Trust and the World Health Organization, to help create antibody production lines using CHO cells for Mapp Pharmaceutical’s ZMapp antibody,” said Amgen spokeswoman Kristen Davis, in an email to BioPharm International. “Amgen’s commitment will include 12-14 staff, who will work on this project through the end of 2014.”

Cell Type Risk Assessment
CHO cells are the most commonly used mammalian hosts for industrial production of recombinant protein therapies, encompassing products both on the market and in clinical development. CHO cells have mammalian glycosylation sites that have been used for numerous FDA-approved drugs, says Larry Grill, PhD, dean of research at Keck Graduate Institute, which makes them attractive candidates for wide-scale mAb production. “Since FDA has approved so many CHO-cell-produced mAb products, pharmaceutical companies consider them to have less risk,” Dr. Grill told BioPharm International.

While the use of CHO cells over tobacco plants could help scale up production, this method may take significantly more time. Production in mammalian cells also tends to produce lower yields and is associated with higher manufacturing costs, according to an analysis in Manual of Industrial Microbiology and Biotechnology (2). Growing biologic product in plants, rather than amplifying biologics in bioreactors, has been cited as a cheaper option. Scaling up is more easily done in plant models, notes Dr. Grill, as additional greenhouse space can be more easily managed. Plants are typically inoculated through agroinfection and can be harvested in less than two weeks.

Because the quality and the commercial success associated with the production of mAbs depend largely on a CHO copy and its level of viability and productivity, manufacturers must ensure they are optimizing downstream processing to eliminate all potential contaminants. Using plants for the production of drugs reduces the risk of contamination from human pathogens. There are no plant viruses that infect humans and plants do not have prions, which are misfolded protein molecules, says Dr. Grill. Plant bacteria are also not a problem, as they are not known to be pathogenic to humans. Purification for both CHO cells and plants cells, however, will likely require purification with a Protein A column, says Dr. Grill.


Dr. Grill, who has been working with transiently modified Nicotiana plants since the mid-1980s, notes there are no major biosafety concerns of genetically modified tobacco plants. “The plants are grown in a secured greenhouse, transiently altered to produce the mAbs within a short period, and then harvested.  There are no genetically engineered pollen or seeds generated,” he asserts.


1. R. Langreth, "Amgen tests new way to make Ebola drug to boost supply," Bloomberg, Oct. 18, 2014,, accessed Oct. 20, 2014.

2. J. Zhang, “Mammalian Cell Culture for Biopharmaceutical Production,” in Manual of Industrial Microbiology and Biotechnology, R.H. Baltz, J.E. Davies, and A.L. Demain, Eds. pp. 157-178 (ASM Press, 3rd ed., 2010).