Recombinant biologic products versus nutraceuticals from plants - a regulatory choice?

Biotechnology has transformed the potential for plants to be a manufacturing source of pharmaceutical compounds. Now, with transgenic and transient expression techniques, virtually any biologic, including vaccines and therapeutics, could be manufactured in plants. However, uncertainty over the regulatory path for such new pharmaceuticals has been a deterrent. Consideration has been given to using alternative regulatory paths, including those for nutraceuticals or cosmetic agents. This review will consider these possibilities, and discuss the difficulties in establishing regulatory guidelines for new pharmaceutical manufacturing technologies.

Commercialization of new biotechnology: a systematic review of 16 commercial case studies in a novel manufacturing sector.

The 1980s and 1990s saw a major expansion of biotechnology into new areas of science including genomics and recombinant technologies. This was coupled to the widespread emergence of academics into the commercial sector as they were encouraged to spin out companies or commercialize their intellectual property. There were many opportunities to raise investment, and extraordinary success stories were prominent across many areas of technology. The field of plant biotechnology for manufacturing recombinant pharmaceuticals (molecular pharming) emerged and was developed in this period. Like other biotechnologies, this was an exciting new development which offered some very obvious benefits and commercial advantages. In particularly, plant molecular pharming represented a highly novel and potentially disruptive manufacturing technology for recombinant proteins. Twenty-five years on, a series of interviews with senior members of sixteen of the most prominent companies involved in the field provides insight into the original drivers for commercialization, strategic thinking and planning behind key commercial decisions and an insider view into the major reasons for commercial success or failure. These observations and recurring themes identified across a number of commercial ventures remain relevant today, as new biotech companies continue to spin out of the world of academia.

Risk assessment and regulation of molecular farming - a comparison between Europe and US.

In this article, the general principles of genetically modified (GM) plant risk assessment and the regulatory framework for contained use and open field production of plant-made pharmaceuticals/plant-made industrials (PMP/PMI) are described. While significant progress has been made for the containment grown (plant cell culture) production of PMPs, with the first regulatory approval made by the FDA in 2012, the commercialization of medicinal or industrial products produced in the field has yet to emerge in either Europe or the US. In the current paper, we discribe the regulatory environment in Europe and the US surrounding GM crops, and provide case studies for experimental field releases of PMP and PMI producing plants in both regions. Suggestions for reducing the regulatory burden for GM plants will be discussed, also in light of the emerging new technologies to modify the genetics of plants. Since regulations surrounding the commercialization of GM crops are very costly and not appropriate for most of the PMP/PMI applications in Europe, we propose that amendments to the EU Directive 2001/18/EC are necessary to allow for the commercialization of products from GM plants without the need of an 'authorization'. To fully acknowledge the overall outcome of adopting plants to produce PMP/PMI, the conclusion is that broader and more balanced legislative oversight is needed in Europe; while specific legislation is not needed in the US.

Molecular farming of pharmaceutical proteins using plant suspension cell and tissue cultures.

Plants have been used for more than 20 years to produce recombinant proteins but only recently has the focus shifted away from proof-of-principle studies (i.e. is my protein expressed and is it functional?) to a serious consideration of the requirements for sustainable productivity and the regulatory approval of pharmaceutical products (i.e. is my protein safe, is it efficacious, and does the product and process comply with regulatory guidelines?). In this context, plant tissue and cell suspension cultures are ideal production platforms whose potential has been demonstrated using diverse pharmaceutical proteins. Typically, cell/tissue cultures are grown in containment under defined conditions, allowing process controls to regulate growth and product formation, thus ensuring regulatory compliance. Recombinant proteins can also be secreted to the culture medium, facilitating recovery and subsequent purification because cells contain most of the contaminating proteins and can be removed from the culture broth. Downstream processing costs are therefore lower compared to whole plant systems, balancing the higher costs of the fermentation equipment. In this article, we compare different approaches for the production of valuable proteins in plant cell suspension and tissue cultures, describing the advantages and disadvantages as well as challenges that must be overcome to make this platform commercially viable. We also present novel strategies for system and process optimization, helping to increase yields and scalability.