After several early problems, plant-made biopharmaceuticals are once again attracting attention. Technologies developed by a new generation of biotech companies could help the market achieve commercial maturity, writes Frédéric Ors.

While several plant-made biopharmaceuticals (PMBs) have entered clinical trials, the predicted results have yet to materialise. The idea of large-scale agricultural production of biopharmaceuticals in fields is expected to take hold, and PMBs have met with opposition from environmentalists and food industry groups on health and safety issues.

However, after a lull in the early hype, PMBs are making a comeback. In the last few years, a new generation of companies has evolved the initial agricultural production concept to offer a new solution that delivers plant-based manufacturing in controlled and confined environments. Since then, PMBs have taken off once again.

The traditional mission of pharmaceutical manufacturing is to ensure continuity of supply at minimal risk and cost. Biomanufacturing requires a high level of technical expertise and capital investment, and the ability of CMOs to meet capacity demand has fluctuated since the early days of biotech. In the late 1980s, the lack of products (antibodies took longer than expected to go through clinical trials and market) resulted in excess manufacturing capacity, putting CMOs in a weak position.

In contrast, five years ago, the knowledge that the biopharmaceutical industry was facing a worldwide ‘capacity crunch’ created a boom in the CMO market. The attractiveness of PMBs is largely determined by the ups and downs of biologic manufacturing capacity. For example, when Enbrel’s shortage was perceived as symptomatic of a crisis in manufacturing capacity, industry experts naturally pointed to transgenic plants as a solution.

In 2006, things look a little different. Current capacity appears to be satisfactory for existing products, and manufacturers are planning modest growth of their capacity over the next five years. Nonetheless, the need to secure sufficient capacity to meet uncertain demand remains a major planning issue and risk factor for biotech companies. This is also a significant incentive to seek alternative means of manufacturing and a real opportunity for PMBs.

PMBs could potentially save the industry substantial amounts of time and money, enable scalable production, and produce complex proteins that current systems cannot. As a result, there has been considerable interest in the development of plants for the production of recombinant proteins in fields. But the advantages of agricultural-scale production (low capital equipment costs and high volumes) can be outweighed by the variations in product yield and quality as well as the difficulty in applying good manufacturing practices.

To avoid these limitations, Medicago and others (see Table 1) have developed second-generation, high-yield production technologies allowing plant-based biopharmaceutical production in confined environments (such as greenhouses or bioreactors). Medicago and Biolex have already built the first examples of cGMP manufacturing facilities and are leading the sector towards clinical trials.

Where to next?

Thanks to this new generation of companies, the PMB sector once again finds itself at a crossroads. Technology is mature, R&D efforts are directed toward scale-up for clinical and commercial production, and the first products to market are expected in 2008-10. Critical size and solid financing will be needed to achieve commercial maturity, and this will lead to further consolidation in this field.

Increasingly, biotech companies will be required to adopt best practice in manufacturing in order to maintain competitive advantage. With a new generation of companies entering the market, the PMB sector is far better positioned for success.