Molecular Farming in Plants: The Long Road to the Market
Recombinant proteins can be produced on a commercial scale using a diverse array of host systems based on microbes, animals, and plants. Commercially established processes have resolved to a small number of standard platforms, including the bacterium Escherichia coli, the yeasts Saccharomyces cerevisiae and Pichia pastoris, and certain well-characterized insect and mammalian cell lines. In contrast, many different plant-based systems have been developed and only in the last few years have standardized platforms begun to emerge. The diversity of plant-based platforms has been advantageous to molecular farming by helping to overcome technical issues, but the failure to focus on specific platforms has made the transition from experimental development to a viable commercial process a long and difficult one. As well as the technical and economic principles required to develop a viable manufacturing processes, plants have also been held back by the lack of a harmonized regulatory system for plant-derived pharmaceutical products, such that much of the early commercial development of molecular farming focused on non-pharmaceutical proteins. Despite these hurdles, pharmaceutical molecular farming is now firmly established in the market, and we are witnessing the dawn of a new age in which plants are regarded as competitive platforms for the commercial production of diverse recombinant pharmaceutical protein products.
We acknowledge funding from the EU projects Pharma-Planta (LSHB-CT-2003-503565) and CoMoFarm (227420), the COST Action Molecular Farming (FA0804), and the ERC advanced grant Future-Pharma (269110).
- Buyel JF, Kaever T, Buyel JJ et al (2013a) Predictive models for the accumulation of a fluorescent marker protein in tobacco leaves according to the promoter/5’UTR combination. Biotechnol Bioeng 110:471–482Google Scholar
- Buyel JF, Woo JA, Cramer SM et al (2013b) The use of quantitative structure–activity relationship models to develop optimized processes for the removal of tobacco host cell proteins during biopharmaceutical production. J Chromatogr A 1322:18–28Google Scholar
- Buyel JF, Gruchow HM, Boes A et al (2014) Rational design of a host cell protein heat precipitation step can simplify the subsequent purification of recombinant proteins from tobacco. Biotechnol Bioeng 88:162–170Google Scholar
- EMEA (2002) Committee for Proprietary Medicinal Products (CPMP). Points to consider on quality aspects of medicinal products containing active substances produced by stable transgene expression in higher plants (EMEA/CPMP/BWP/764/02). EMA, London, UKGoogle Scholar
- EMEA (2009) Committee for Proprietary Medicinal Products (CPMP). Guideline on the quality of biological active substances produced by stable transgene expression in higher plants (EMEA/CHMP/BWP/48316/2006). EMA, London, UKGoogle Scholar
- FDA/USDA (2002) Draft guidance. Drugs, biologics, and medical devices derived from bioengineered plants for use in humans and animals. FDA, Rockville, MD. http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM055424.pdf
- International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) (2012) Q11. Development and manufacture of drug substances (chemical entities and biotechnological/biological entities). Fed Regist 77:69634–69635Google Scholar
- Ogawa M, Kumamaru T, Satoh H et al (1987) Purification of protein body-I of rice seed and its polypeptide composition. Plant Cell Physiol 28:1517–1527Google Scholar