Brazilian plant to make Humira biosimilar in 'tobacco-based bioreactors'

A tobacco plant-based platform could make monoclonal antibodies up to 90% cheaper than mammalian systems, says Axis Biotec which is building a pilot plant in Brazil.

Brazil-based Axis Biotec Brasil, in a joint venture with Canadian biotech PlantForm Corporation, is set to commence construction on a pilot production facility in Rio de Janeiro, Brazil to support the development of a biosimilar version of AbbVie’s best-selling mAb Humira (adalimumab), along with several other pipeline biologics.

The plant will cost around $750,000, project coordinator Lorena Diniz told Biopharma-Reporter and will house PlantFORM’s vivoXPRESS platform – an expression technology based on Nicotiana benthamiana plants.

“The technology is used to produce fully active recombinant proteins and antibody drugs at low cost in tobacco-plant-based ‘bioreactors,’ meaning the plants will be used as individual factories themselves,” Diniz said.

The plants are grown in a fully contained, hydroponic system for controlled transient expression of recombinant proteins in clonal population of the tobacco-related plants, she continued.

“This expression platform has been linked to a downstream process system, analytical characterisation, and assessment of biological activity. Purification of the tetrameric IgG antibody will be effected by standard industrial strategies using affinity chromatography capture, orthogonal ion exchange chromatographic methods, and cross-flow filtration.”

‘Weeks rather than years’

According to Diniz, the platform will allow for rapid development of both the adalimumab molecule, along with other monoclonal antibodies in Axis’ pipeline – “taking weeks rather than years” – while also offering a number of technical and cost advantages over mammalian cell-based systems.

These include: “High-throughput development and screening of candidate product molecules, ease of both primary amino acid sequence manipulation and glycosylation engineering, rapid drug development timeline, high levels of drug expression, unlimited scale-up capability, plus low-cost manufacturing up to 90% lower than mammalian cell technology systems.”

A common way to produce therapeutics and vaccines in the next 10 years’

Axis and PlantForm are not alone in using plant-based systems to produce biopharmaceuticals.  The experimental Ebola therapy ZMapp, composed of three monoclonal antibodies, was being produced in tobacco plants by CMO Kentucky Bioprocessing. Israeli firm Protalix, meanwhile, uses expression systems based on genetically engineered tobacco and carrot cells for its biologics pipeline, and Mitsubishi Tanabe is trialling an influenza vaccine made in tobacco plants.

“Plant transient expression is a recognized flexible and affordable method for drug development, which can be scaled up more rapidly than any other recombinant expression systems,” said Diniz.

“The safety, efficacy and potency of generated products will facilitate development of pharmaceuticals needed to address public health issues. This technology has a huge potential and could be a common way to produce therapeutics and vaccines in the next 10 years.”