During the 90's, then-very young plant-factory organizations saw big pharma as the Holy Grail - distant, unreal, the panacea to all the growing pains of a young industry. The expectations have become more realistic over the years. Plant-factory companies have tended to mirror the biopharma sector in chosing between partnering, self-product development or the CMO model. Still, Big Pharma plays an important role in PMP's future. What do pharmaceutical companies think of plant-factories? And what are the long-term perspectives of biodrugs production?

As an encore to Québec City, the update of the acclaimed "State of the market" presentation (biopharmaceutical's current market and pipeline).

What pharma organizations consider before making billion-dollar manufacturing investments in facilities for biologics, from a man with a bias toward stainless steel. We will hear about the risks of new systems, especially in view of possible improvements in yields in this 20 year-old technology.

The best selling drug of 2015 is, as your read this, somewhere between the bench and pre-clinic trials. Maybe it is expressed in a plant-host. But who knows if big pharma as we know it, will develop it? We have heard from Mr. Burrill provocative concepts like the "Dead Blockbuster", preventative medicine and a new era of diagnostic/personalized treatments, the risk-based mutations of FDA and of course, the demography of patients and the financial markets. We asked Mr. Burrill to look into his crystal ball, with the future of production-systems in mind.

To metamorphose from manufacturing operations to full-members of the pharma industry, plant-factories need money. But, even more, they need marketable drug candidates be those candidates for orphan indications or be they blockbusters in the same class as Embrel, Factor VIII, Insulin and Remicade. Chaired by a man who digs deep into the human genome to find the products of the day after tomorrow, this session takes on tomorrow's drugs, leads us into less known territories to be conquered by PMP organizations, and looks at the potential and challenges of promising product classes.

Producing recombinant proteins in heterlogous systems is not easy. There are three main reasons for the absence of biologically active protein expression. Firstly, the expression host may lack components of translational machinery or the structure of mRNA is not conducive to high-level translation. Secondly, the heterologous protein is prone to proteolysis as soon as it emerges from translation - often the host system is programmed to degrade the heterologous protein thus reducing the yield of protein. Thirdly, the protein does not fold correctly to allow biological function (lack of chaperone or of correct post-translational modifications). One of the organizers of a "Difficult-to-Express Proteins" conference (CHI, May 2005), this presenter will show that each difficult-to-express protein represents its own problem. This problem may require a customized solution and that increasing the yield of protein in heterlogous system is generally part of the solution. Examples will be given, including fusion proteins such as the SUMO system or other state-of-the-art fusion and cleavage systems. The thrust of this presentation is to explore ways to reduce the cost of production for biologically active proteins.

The clinical trials for the antibodies discovered by Prof. Katinger could confirm the existence of a solution to AIDS - however, these microbicides and active vaccines would be needed by the ton. This presentation will first discuss the challenges of low-cost production platforms, especially the productivity threshold that plant-factories must achieve. Second, Prof. Katinger will describe other antibodies on the horizon that could be a match with the nature of plant-factories, including those amenable to dermal or mucosal administration of partially purified compounds.

Speculation abounds in the pharmaceutical and biologics industries about the possibility of the U.S. Food and Drug Administration implementing an abbreviated regulatory approval route for biogenerics, and, if such an abbreviated route were implemented, what form it might take. This presentation will outline the background, arguments for and against, and likely outcome of this debate, as well as its potential implications for plant-made pharmaceuticals. Specifically, this presentation will focus on the regulatory issues surrounding the possible creation of an abbreviated FDA approval route for a biogeneric. It provides an overview of the abbreviated approval routes already in place for the review of chemically synthesized small-molecule drugs under the current U.S. regulatory framework, and assesses the regulatory arguments being made for and against the use of such a pathway for biogeneric pharmaceuticals. It will also analyze these arguments in the context of plant-made pharmaceuticals specifically. In addition, the presentation outlines the current thinking on the likely outcome of the biogeneric debate, and reviews the various types of data packages that have been presented to the U.S. Food and Drug Administration as possible solutions to the current impasse. Though much of the presentation of legal issues will focus on U.S. law, it will also include a comparison of current U.S. law to regulatory frameworks in the EU and in other countries. Finally, the presentation concludes with thoughts on the “hot” biogeneric drug candidates most likely to be pursued by industry in the next few years and the consequent demand for active ingredients that will necessarily follow from such pursuit.

You want to produce a great compound or to acquire a promising technology. This practical session, from a scientist (plant-made oral-administration vaccines) turned patent specialist during his years with Mycogen, will explain how to make sure that what glitters is gold, before you commit to an in-licensing or acquisition agreement.

Purifying recombinant proteins from plant material can be seen as a challenge (doing as well as CHO's), or as an opportunity (plant-specific capacity). This session will show how plant hosts, both from seeds and green tissues, can do as well or better than cell lines.

A prospective review based on the article "Considerations for the Recovery of Recombinant Proteins from Plants" (June 2004).

This presentation will summarize the potential impact of terrestrial and aquatic transgenic plant technologies on the key drivers for the biopharmaceutical industry, Time-to-Market, Cost-to-Build and Cost-of-Goods, relative to CHO, E. coli and other biopharmaceutical product sources. A comparison will be made between the pre-chromatographic processes for these product sources relative to the above drivers. The presentation will also include a discussion on downstream process options for transgenic plant technologies and the development of an “ideal” biopharmaceutical process based on these sources, non-chromatographic technologies for initial purification, continuous liquid chromatography for final purification and a new continuous process support system design. The presentation will conclude with a discussion of near term objectives for transgenic plant technologies.

This presentation will discuss the post-harvest recovery and purification of therapeutic biologics from green leaf tissue. The downstream processing considerations for several known plant expression systems will be reviewed. Potential compliance issues and process analytical technologies (PAT) will be highlighted and several examples of specific protein categories will be presented. The paper will discuss the development of a regulatory bio-processing strategy, the presentation of release criteria to the FDA, and how to develop the CMC section of a potential IND or BLA.

In any protein-production system, increasing the production scale can significantly reduce production costs on the upstream side, but not on the downstream side. Downstream cost will remain the bottleneck for a further reduction of costs, since no economy of scale is possible at the moment for the selective units (e.g. chromatography, membrane and extraction units). These bottlenecks could be opened by the development of highly selective materials by design, which would be capable of processing large-scale amounts at reasonable costs.

The balance between providing a manufacturing platform for licensing – a CMO model – and developing your own products, is gradually shifting. Companies (and their investors) are discovering the difficulties of deriving value in a timely manner from partnerships. Some companies are responding by shifting the focus to developing products; another approach is to broaden the technology and diversify. In this session chaired by Mr. André Archimbaud, the representative of SGF, the main industrial investor in Québec, a panel of VCs, bankers and entrepreneurs, assembled by Dr. Håkan Telenius of MDS Capital, consider the business models and challenges in financing the different stages of a company’s development.

One of the only real challenges of an PMPs is time, because the prizes will go to those who complete the whole product approval marathon. Dr. Håkan Telenius is assembling a group of VCs, brokers and CFOs to consider the investments needed to support various models (product development, contract manufacturer, technology provider) toward profitability. The foreseeable financing climate and realities from seed to stock markets will be explored, and means to diminish the risk factors that compound the value of PMP companies will be suggested.

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First of two high-level sessions that showcases productivity tools to save time, improve protein quality and generate cost savings. The tools discussed include plant transformation systems, transient expression (viral and bacterial) and metabolic engineering.

A key element in any program that encompasses applications of plant biotechnology is an efficient technology for introducing transgenes into plants. Gene transfer technology and the fate of introduced transgenes post transformation thus constitute an essential early step in any plant biotechnology program. Understanding transgene integration mechanisms and their implications will facilitate the development and implementation of novel gene transfer strategies that will be more efficient and more precise than it is currently possible with conventional methodology. Unlike the requirement for the presence of backbone sequences in transformation methods involving biological vectors such as Agrobacterium tumefaciens, the presence of such sequences are not essential for direct DNA transfer. It is now recognised that such sequences often precipitate rearrangements that frequently lead to transgene inactivation. This is more frequent in species with more complex genomes such as cereals and legumes. A recent development in direct DNA transfer is the use of ‘clean DNA’ cassettes that comprise only the minimum essential expression components of the transformation vector, i.e. promoter, coding sequence and terminator. This technology has now been extended to co-transformation of up to 5 different transgenes and there is no reason to believe that this constitutes an upper limit in terms of the number of input transgenes. Fluorescence In Situ Hybridisation (FISH) and confocal microscopy in conjunction with molecular DNA analysis are currently being used to study the organisation of transgenic loci and this allows us to define in detail factors that may play a positive or negative role in terms of levels and stability of transgene expression. We will discuss in some detail the latest innovations in plant transformation technologies and focus on aspects of such technologies that provide clear advantages for applications such as the engineering of complex metabolic pathways and the assembly of multimeric proteins for molecular pharming.

Agro-infiltration has become a powerful tool for the industry of plant-made pharmaceuticals. From the rapid demonstration of the capacity to accumulate specific proteins in plants, to the small-scale production of therapeutics, the method has been