As I wrote last month, using plant cells to make biopharmaceuticals is not a new idea. However, while several plant-made biopharmaceuticals, including treatments for diabetes, hepatitis, and an Ebola vaccine, have been approved, the vast majority are still produced in cells culture in bioreactors.
And this means biopharma is missing out according to Randy Maddux, COO of iBio, who cites scalability, the absence of mammalian viruses as well as cost reduction as advantages of a plant-based expression system.
“Cost advantages come in the form of lower CapEx to build the upstream, and lower overall company costs to go from hit to IND, given months are saved as we take manufacturing off of the critical path,” he says. “The speed advantage to manufacturing GMP material will get new medicines to patients faster.
“The biggest surprise is how quick it is (by virtue of avoiding having to create a master cell bank) and how the scale-up issues can be avoided (each plant is a standard-sized bioreactor, so the scale-up is digital. Want more product? Just grow more plants.”
Controlling production parameters is also more straightforward in a plant than in a bioreactor, according to Maddux, who points to iBio’s plant-based drug production facility as an example.
“Our GMP facility in Bryan, Texas uses vertical farming with automated hydroponics under controlled lighting conditions to deliver therapeutic proteins with batch-to-batch consistency,” he explains.
Modifications
Another potential advantage of a plant-based expression system is that the mechanisms and processes for inserting DNA are already well established and understood Maddux says, again citing iBio’s own approach as an example.
“We mobilize the vector by inserting it into a species of Agrobacterium that gets vacuum infiltrated into the plant leaves to convert the Nicotiana benthamiana plant into a bioreactor,” he tells GEN. “Agrobacterium is a gram-negative micro-organism, which means plenty of endotoxin to watch out for. However, iBio and others have managed that challenge so that it’s not a significant difference vs. traditional bioprocessing.”
The practice of strain engineering—breeding plants so that desirable traits are retained and amplified in subsequent generations—is well established, which is also likely to be useful for drug manufacturers.
“Another factor positioning plant-based production for future success is the wider availability of plant hosts with different properties; for example, to modify glycosylation of produced proteins,” says Maddux. “The benefits of strain engineering are increasingly available in plant-based systems, which will increase versatility going forward.”
