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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 2 - PlugBioIn (Plug and play enzymes for an accelerated uptake of Biocatalysis in the Pharmaceutical Industry)

Teaser

Summary

At present there is a mismatch between the extensive interest of the pharmaceutical industry to utilize enzyme technology in their production processes and the number of such processes commercially implemented. To overcome this mismatch c-LEcta aims at offering a smart platform of Plug & Play enzymes for the three most relevant enzyme classes (alcohol dehydrogenase, transaminases, and nitrilase). The platform will address the needs of the pharma industry for performing essential biocatalytic reactions suitable for the production of million fold applied chiral active pharmaceutical ingredients (APIs) like Atorvastatin, Rosuvastatin and Duloxetine. The API market is valued at $101.08 billion in 2010. The unique selling proposition of this platform is to comprise ~100 high quality enzymes per class, which are pre-qualified for a wide range of important structural patterns, applicable for synthesis processes and easily scalable. Therefore, the business opportunity is to take advantage of the great potential of biocatalysis since the platform allows matching timelines and cost requirements. Up to now such service was not available without contract signing and extensive development timelines and costs. The development cost may be reduced up to ~80% by using the new platform technology compared to the conventional work flow. In manufacturing, the total production cost of a product will be typically reduced by >30%. The platform will be promoted to a medium volume market with high growth rates. c-LEcta will address the global market, which is going to be widened step-by-step. Subject matter of Phase 2 c-LEcta is to refine the design of the enzyme platform, to scale up the enzyme production, synthesis process development and pilot-scale application in order to demonstrate and to assure rapid availability of enzymes in pharma development and for subsequent commercialization.

Work performed

The essential part of our product is sets of prequalified biocatalysts that can be easily implemented by the pharmaceutical componies. We developed collections of enzymes the three most frequent demanded enzyme classes which are alcohol dehydrogenases (ADH), transaminases (ATA) and nitrilases (NIT). The sole availability of enzyme collections was not enough to convince (pharmaceutical) industry to use enzymes instead of chemical catalysts in their process and accordingly we demonstrated the preparative synthetic application of the enzymes and established scalable production processes for the biocatalysts. This upgrades an enzyme collection to â€œPlug & Play Biocatsâ€, a name that we trademarked. The experience we gained from applying the enzymes in preparative reactions were put down on paper in a language that can be understood for customer that have not been using enzymes before. These guidelines are used upon customer contact to support the operator to implement our product successfully.
The results were disseminated on scientific and more business oriented conferences in oral lectures and on booths with purpose-made flyers. The product was also featured in two webinars, which attracted a broad community. A webpage was created at the product section of c-LEctaâ€™s homepage to provide information, a contact address and finally an online ordering tool for the product. The direct communication with customers was highly valuable to adjust our offers and services. Other technology services of c-LEcta, like enzyme production or a custom enzyme development, could be addressed as well with these communications. The â€œPlug & Play Biocatsâ€ thus serves as an attractant for our further services as well and helps to strengthen our business.
Scientific papers featuring the â€œPlug & Play Biocatsâ€ were realized with academic and industrial colleagues. Those publications from independent researches present the uniqueness and advantages of our enzymes and gain important impact in the community. A notable work was published by scientist from Pfizer (which is among the world\'s largest pharmaceutical companies) who did a comparative study with enzyme collections from various providers and rated our ATA and ADH enzymes as the most useful for their application.
The main exploitation system is the provision of the enzymes collection in small scale format which is used by the customers in screenings. This entry point should be as simple as possible. Accordingly, the prices for the enzymes in small scale were reduced in order to make costs no hurdle for the companies to implement our enzymes in their screen. Our aim is that the enzymes end up as a hit and negotiations of large scale provision of our product can start. Unfortunately, this has happened less frequent than we had expected. This is partially due to slow implementation of new products by the pharmaceutical companies. Since we entered several agreements meanwhile and the quality of the product developed in this project is getting very positive feedback from the community, we expect that a constant increase in sales in the coming years will take place.
In summary, we developed a high quality set of enzymes which are now routinely used by the main pharmaceutical companies. This is a great success of the development we could realize within the PlugBioIn project and will help us to realize sustainable business in the near future.

Final results

The access to high quality biocatalysts that are specifically developed to be applied in the pharmaceutical industry has multiple impacts beyond the state of the art. Biocatalysts are in several instances superior to chemical catalyst. Not only is the performance often superior (higher yields, less side products, simple reaction conditions) which has a direct economic impact. They also deliver processes which are much greener in the sense that less toxic or environmentally hazardous materials need to be used. This has also direct impact to the human health of the workers in the production sites. In addition to improved performance, the biocatalyst offer routes to more effective synthetic routes or even new chemical entities.
The development in this project is thus strengthening the biotechnological and pharmaceutical industry in providing superior processes and economical savings. Moreover, it delivers environmentally more friendly processes with direct impact on the ecosystem and human health.