Biotech drug production techniques based on plants, which may prove to be faster, higher yielding and cheaper than current methods using mammalian cells, haven't caught on with the biggest pharmaceutical companies.

The leading players in so-called "plantibodies" include San Diego's Mapp Pharmaceutical, which garnered global attention for an experimental Ebola drug given to two American medical workers, as well as companies like Germany's Icon Genetics, Canada's PlantForm Corp, and Delaware-based IBio Inc. All of the privately-held companies are working to produce antibodies, protein drugs and vaccines in fast-growing plants.

These companies hope the lower cost of plant-based production -- in some cases as little as one-tenth the expense of conventional antibody manufacture -- will eventually capture the attention of larger drugmakers. Big pharmaceutical makers have yet to embrace the technique after spending hundreds of millions of dollars on their current manufacturing lines.

Industry experts say large drugmakers also need evidence that the process can pass muster with regulators who have yet to approve a biotech drug produced completely from plants.

"I think the interest will come," said Victor Klimyuk, chief operating officer at Icon Genetics. "It's typical that the Big Pharma industry is very conservative in what they establish and what they invest in."

Bayer AG in 2010 joined with Icon to launch early-stage human trials of a cancer vaccine grown in tobacco plants, but the larger healthcare company has since dropped out.

Bayer declined to comment on why it decided not to pursue the venture. Icon's Klimyuk said Icon is seeking a partner to move the personalized vaccine into mid-stage trials.

"Our technology can complement standard manufacturing techniques," Klimyuk said. "It may work best when speed is required or when flexibility is required ... to manufacture vaccines for an epidemic or for fast, reliable production."

FROM METAL VATS TO GREENHOUSESAntibodies are proteins used by the body's immune system to block the path of foreign, potentially damaging invaders.

There are around 30 antibody-based drugs on the market in the United States - including blockbuster cancer therapies such as Avastin and Rituxan, both from Roche Holding AG. They are all produced from mammalian cells, often from hamsters, that are cultivated in large stainless steel vats.

"The technology in use now is very established and extremely efficient … the big companies have made those investments and adopted those systems," said Michael Kamarck, a biotechnology industry consultant and former manufacturing executive at Merck & Co Inc, referring to mammalian cell cultivation. "But if you are a small biotech with a great idea, it might make sense to use the tobacco plant to quickly produce antibodies for testing."

So far, the one successful venture into plant-derived drugs is a U.S.-approved therapy for rare disease made by Israel's Protalix Biotherapeutics, and marketed with Pfizer Inc.

The drug, Elelyso, is an enzyme produced from genetically engineered carrot cells, but the cells are not reproduced in the plants. They are replicated in a closed system using disposable plastic bags.

"We actually use cell culture - carrot cells or tobacco - in a way that is similar to what is done in growing mammalian cells for the biotech industry," said Protalix CEO David Aviezer.

He said the method - which Protalix is using for a range of experimental drugs - is less expensive than producing drugs from mammalian cells, but has the benefit of a clean-room environment that regulators expect to see and are familiar with.

The U.S. Food and Drug Administration has signaled some of its concerns over plantibodies, including the need for manufacturers to demonstrate that the source plant produces a consistent product.

In draft guidance from 2002, the agency also cited the potential for the plant to express an allergenic or toxic compound and the need to ensure that plant propagation is contained.

Pfizer, in an emailed statement, said it is not focusing on producing drugs in plants. Gilead Sciences Inc and Amgen Inc, the world's two largest biotechnology companies in terms of revenue, said they had no information on the topic. Genentech, the biotech arm of Roche, said it does not manufacture proteins from plants.

"Developing new drugs is a very expensive and risky business,' said Qiang Chen, a professor at Arizona State University currently researching the use of plant-farmed antibodies against the West Nile virus. "I understand why they don't want to jump into new technology that will make their lives potentially more risky."


Executives deeply involved in plantibodies say their work has come a long way toward viable production.

"Fifteen years ago there were a number of companies involved, but none were particularly successful," said PlantForm CEO Don Stewart. "Yields were not that impressive and time lines to development were quite long."

Mapp's drug, ZMapp, consists of a "cocktail" of antibodies produced in tobacco plants at Kentucky BioProcessing, a unit of cigarette maker Reynolds American. The process involves inserting antibody-coding genes into the plant and growing them inside the leaves, which are then harvested and ground up to extract the antibodies.

PlantForm's Stewart estimated that for some protein drugs, the cost of plant-based production could be one-tenth the cost of traditional biotechnology manufacturing.

That could help poor countries like Liberia, among the hardest-hit in the current Ebola outbreak, as well as developed nations where healthcare costs are outpacing economic growth.

"We see it having pretty broad applicability," Stewart said. "The cost of these drugs is a huge burden on healthcare systems in the first world, particularly drugs for oncology and chronic disease."