Plant expression systems are emerging as fast and inexpensive methods for producing vaccines. Someday, plants may surpass mammalian and even many microbial systems in efficiency and cost-benefits for the manufacture recombinant proteins. This is particularly so for the rapid manufacture of truly large-scale (million- or even billion-dose) vaccine antigens. Whether grown as single cells or tissues in photosynthesis reactors, as whole plants in controlled laboratory situations, or cultivated in fields of transformed food-commodity plants (e.g., rice, potatoes, or tobacco), plants being adapted for recombinant protein manufacture offer high yields and relatively low investment costs. These systems can move quickly from identification of a candidate to expression, testing, and manufacture.

According to our recent study, a wide variety of plant-based expression systems are being used for manufacturing products — often vaccines — currently in the development pipeline (1). Many cell culture processes are using plant-expressed products such as Cellastim recombinant human serum albumin (rHSA) from Invitria. However, global concerns in scaling up vaccine production for influenza outbreaks paired with biodefense threats have mobilized record-level amounts of US governmental funding toward developing new vaccine techniques and technologies.

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Game-changing developments in the commercial environment of plant-based expression systems used for vaccines manufacture are poised to affect the bioprocessing industry as well. Transition of vaccine production from familiar mammalian cells, bacteria, and yeast technologies to plant-based expression systems is a fast-breaking arena, which mandates knowledge of not only key new technologies, techniques, and partnerships, but also how to handle their industry-wide impact. As the biotech industry as a whole begins to learn of this potential, those working with vaccines know of plants’ recent significant commercial viability.

The US$5.9 billion/year biodefense plan's new strategy provides funding for new, rapid-manufacturing– oriented bioprocessing platform technologies that apply to a wide range of infectious disease threats. Those include bioterrorism (anthrax), pandemics (influenza), and infectious diseases that affect the developing world (e.g., malaria). In vaccine-specific development, the US Health and Human Services (HHS) National Institutes of Health (NIH) — particularly though its National Institute of Allergy and Infectious Diseases (NIAID) — is broadening the types of technologies it pays to develop.

The vaccines industry couldn't have had a better indication of the need for new flu vaccine technology than its 2009 experience with the H1N1 virus. At a December 2009 conference, HHS secretary Kathleen Sibelius said, “There was one fundamental problem we couldn't overcome: We were fighting the 2009 H1N1 flu with vaccine technology from the 1950s… [The] vaccine grew slowly in eggs… We've talked about updating our vaccine technology for years” (2).

A Knowledge Gap

Plant-based expression systems for vaccine production are already on a fast track, with regulatory approvals expected over the next several years. These systems are likely to become larger players in the $20 billion/year worldwide vaccine industry that is projected to top $35 billion in five years. Despite the advances, however, several significant factors are stalling wider bioprocessing industry adoption of new plant expression systems in this highly technology-transferable area:

• Difficulty of gaining the requisite bird's-eye view of these diverse and global trends and developing a knowledge base sufficient to support adoption of new technology

• Complexities in translating technical analyses into organizational change (whether in the laboratory, facility, or fields, using plants requires different skills and experience, and few bioprocessing professionals are yet familiar with these plant technologies).

That knowledge gap is demonstrated by the relatively few companies exploring these technologies for commercial production — particularly outside the vaccine and biodefense areas, where plant expression for regulated product manufacture is being pioneered. BioPlan's recent survey of biopharmaceutical manufacturers illustrates the knowledge gap. Only 14% of respondents plan to increase manufacturing using plant expression systems in the next five years. Only 10% projected using them to expand manufacturing capacity by >100%. And most companies planning capacity expansions will continue focusing on mammalian cell, bacterial, and yeast expression technologies instead.

Given the diverse changes and the challenge of integrating plants into a corporate strategy, essentially requiring companies to rethink their upstream manufacturing processes, bridging this information gap can require radical thinking. New manufacturing strategies will be necessary for assessing and integrating new technologies and participating in R&D opportunities such as the Defense Advance Research Product Agency's (DARPA's) biodefense programs and the HHS Biomedical Advanced Research and Development Authority (BARDA) initiatives managed by NIAID and NIH.