Interest in “molecular farming”—using plants to make therapeutic proteins—is growing, all puns intended. The surge is thanks, in part, to new technologies that offer the chance to scale production without the need for a larger manufacturing footprint.
Plants and plant cell-based expression systems offer advantages over mammalian-, insect-, bacterial-, or yeast-based systems. For example, unlike CHO cells, plants do not support the growth of viruses that are harmful to humans.
In addition, while most biopharmaceuticals are made in mammalian cells, several plant-made products have been approved—Protalix’s Gaucher’s disease drug Eleyso, for example—which means regulators are becoming more familiar with them.
And this is good because interest in molecular farming is growing, according to Don Stewart, CEO of Canadian contract manufacturing organization, PlantForm.
“There are many pharmaceutical products which have successfully completed clinical programs in humans and several which have been formally approved by FDA for commercial sale,” he tells GEN.
Stewart cited Medicago’s use of an engineered variety of Nicotiana benthamiana, a weed native to Australia, as an example of commercial-scale molecular farming.
“Medicago developed influenza and COVID-19 vaccines using whole plant manufacturing. Similarly, Israel-based regenerative and aesthetic medicines company Collplant has a commercial collagen product made in whole transgenic plants,” Stewart says.
Processing
Another advantage of molecular farming is that the technologies and processing steps are very similar to those used in traditional biopharmaceutical production, particularly in downstream operations.
Stewart says, “Downstream product recovery from whole plant and plant cell expression systems is essentially identical to conventional systems following extraction and clarification.
“And, while upstream operations for whole plant expression systems are significantly different, the extraction and filtration methods are essentially identical.”
PlantForm’s production activities are based on vivoXpress, a proprietary technology designed to make it easier, faster, and less expensive to manufacture biologic drugs.
At present, PlantForm is working on a biosimilar version of the cancer drug Keytruda in collaboration with Brazil’s Bio-Manguinhos/Fiocruz and Belgium-based molecular farming biotech, SwiftPharma.
Facility design
Molecular farming also offers benefits from a manufacturing facility design perspective.
Many commercial molecular farming operations use vertical hydroponic cultivation beds, which—in addition to being simpler and cheaper to operate than traditional bioreactors—have a smaller footprint, according to Stewart.
“Modern vertical farming operations have a footprint similar in scale to conventional biopharmaceutical, cell-based, facilities,” he says.
Also, vertical cultivation offers flexibility in terms of the ability to respond to demand fluctuations, according to Stewart.
“Increasing scale can be readily accommodated by increasing height—adding more layers for plant growth—rather than expanding the footprint area,” he adds.