Using plant cells to make biopharmaceuticals is not a new idea. Pfizer’s Gaucher disease drug Elelyso (taliglucerase alfa), which is manufactured using carrot cells in culture—was approved in 2012.

Whole plants are also used to make biopharmaceuticals. For example, last year, the FDA approved Palforzia (AR101), an oral peanut-protein immunotherapy developed by Aimmune Therapeutic.

The approvals are indicative of a growing recognition of the role plants can play in biopharmaceutical manufacturing, says Matthew McNulty, PhD, from the department of chemical engineering at the University of California, Davis.

“The biopharmaceutical industry has been slow, but not entirely resistant, to embrace plant-based manufacturing, which is also known as molecular pharming,” he continues. “However, evidence and recent trends suggest that plant-based manufacturing is indeed gaining traction in the industry.”

McNulty points to Medicago, which uses plant-based systems to make vaccines and DARPA’s $100 million plant-based biopharmaceuticals initiative as further evidence of industry’s willingness to embrace the approach.

Growth process

Plant-based production—using whole plants or cells—has many potential advantages from a bioprocessing perspective, adds Karen McDonald, PhD, professor, also in the department of chemical engineering.

“There are many different ways in which plants or plant cells could be used in biopharmaceutical manufacturing, ranging from using outdoor, field-grown plants to growing plant cells in liquid suspension in bioreactors, but also including intermediate approaches such as plants grown in greenhouses, or in indoor vertical agriculture facilities,” she explains.

Cost and complexity would vary depending on the specific approach, however, McDonald says, any form of plant-based production would likely be cheaper than traditional biopharmaceutical manufacturing methods.

“Plant cell bioreactors would likely be the most costly of these but would still offer advantages of lower media costs due to the simplicity of the medium composition, elimination of animal sourced components, robustness, biosafety, and potential for long-term operations in continuous or semi-continuous operational modes,” she continues.

Whole plant-based production would also be cheaper, according to McDonald, who says the approach reduces the complexity of upstream equipment and operations, which simplifies supply chain, lowers maintenance costs, and eliminates the need for highly trained operators.

Upstream advantages

McNulty, who with McDonald and colleagues, discussed plant-based biopharmaceutical production in a recent study, also sees upstream operations as the main area of benefit.

“The main difference is that the upstream portion of manufacturing will now consist of some plant cultivation unit—indoor controlled environment facility, greenhouse, outdoor field,” he tells GEN. “Specific equipment employed for upstream processing with whole plant systems will vary based on the type of plant cultivation used, but may include automated seeders, LED lighting, circulatory irrigation systems, and sometimes specialized vacuum chambers for biopharmaceutical gene delivery to the plants.

“The first couple processing steps to grind up the whole plant tissue and extract the medicine may also look slightly different from traditional biopharmaceutical manufacturing. After this point, the processing of the medicine would proceed in a similar fashion to the process flows employed in typical biopharmaceutical companies.”


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