Clinical trials of a monoclonal antibody produced in transgenic tobacco plants, a potentially low-cost, scalable system, have begun in Europe.
In 2004 industrial and academic partners began work on a system for producing proteins in plants. Delays in development of a regulatory pathway for plant-produced proteins meant the project overran but a manufacturing system is now working and a clinical trial underway.
“We now have a facility in Europe for producing modern medicines in transgenic plants that is unique in the world, although this has taken many years and much investment to establish”, said Rainer Fischer, Pharma-Planta coordinator and Fraunhofer IME director.
Transgenic tobacco plants are grown for 45 days before being processed at a biotechnology facility in Aachen, Germany. Leaves are chopped and shredded in 250kg batches and then undergo downstream processing to extract more than five grams of pure antibody.
As well as developing a practical production system the team had to make sure it was acceptable to regulators and this, according to Pharma Planta, was the most difficult phase of the project.
Pharma Planta worked with regulators to overcome the lack of manufacturing guidelines for production in greenhouses. Greenhouse conditions were tweaked and equipment for purifying the active ingredient from the leaves under GMP (good manufacturing practice) was built and tested.
Paving the way
Having gone through this process and gained UK Medicines and Healthcare products Regulatory Agency (MHRA) approval for a Phase I trial the team think other plant-produced proteins can be developed.
“This is a red letter day for the field. [MHRA approval] is an acknowledgement that monoclonal antibodies can be made in plants to the same quality as those made using existing conventional production systems”, said Julian Ma, scientific coordinator for Pharma-Planta.
Now Pharma-Planta has shown an anti-HIV microbicide, P2G12, can be manufactured in green plants the hope is other products will follow. Widespread use of plant-based production could, say its supporters, ensure an affordable supply of vaccines and other drugs for the developing world.