We transfer cutting edge technologies from the pharmaceutical industry to production processes for bioactive in agriculture. This is enabled by our background in pharmaceutical process development and contract manufacturing and represents our competitive advantage. We have gathered know-how about the close relationship between process parameters and product quality. This know-how greatly increases efficacy in our development cycles. But that is not all, the close cooperation with universities allows us to access the latest analytical technologies and the most advanced expertise from various scientific areas.
To showcase our capabilities, we have picked a challenging target. A symbiotic fungus (AMF) which is capable of increasing fertilizer and water efficiency in agriculture. Read more Following the in-vitro production approach for the sake of product quality and reproducibility, the plant symbiont imposes the greatest challenges to the scalability of AMF production processes. Only if AMF production processes can be pushed to the cubic-meter scale, the associated cost of goods can be decreased to the point which makes AMF an economically viable product.
Hairy Roots – A Scale-Up Breakthrough
INTRODUCTION TO HAIRY ROOTS
Hairy roots are the result of a plant tissue transformation with agrobacterium. In a natural process, the tissue starts growing in form of roots that feature a large potential for the production of complex compounds. Given the natural transformation process, hairy roots are generally regarded as non-GMO organisms. What makes the hair roots really stand out is the fact that they can be directly used, since they are not genetically modified and originate directly from nature. This makes the purification of products a lot easier. To this date, attempts for industrial-scale hairy root production failed to scale above 70L volume despite the significant economic potential. Our novel production approach is based on a revolutionary, patented reactor design. This development allows the upscaling of the hairy root production process to several m3 for the first time.
Conventional reactors were able to cultivate the hairy root only to a limited volume. Evologic built and tested a series of bioreactor prototypes to tackle the critical issues concerning the scale up. Our novel reactor design enabled us to overcome the challenges on the way to industrial scale while providing highly reproducible batch cultivations.
Identification of ideal Reactor dimensions
The geometric dimensions and resulting flow patterns have been optimized in using a computational flow dynamics (CFD) model. Flow patterns and particle behavior are modeled and analyzed. The regular verification of the CFD model with experimental data ensures the validity of our models. This approach helps to save time and costs over a common trial and error approach.
Development of Reactor Set-up
Cultivation of an organism with differentiated tissue like roots poses a lot of challenges. Roots can get stuck, suffocate, accumulate of seizing to grow. The reactor is hard to keep sterile over the long cultivation cycles. Especially the transfer of roots during the scaling steps is critical for sterility. We solved all the problems posed by developing dozens of highly diverse prototypes.
Measurement of hairy root biomass
Quantifying the biomass of hairy roots under 100% sterile conditions is a challenging task. They must not get touched and are very sensitive. For this reason, we developed a conservative technology to measure biomass using computer-assisted image analysis. This allows instant measurements and can even be used for quantifying our first product, AMF.
First product case: AMF
EVOLOGIC PRODUCTION METHOD
Evologics patented Hairy root production process enables the production of AMF in a bioreactor. This bioreactor can be scaled up instead of the usual up numbering. With this approach, very little manual labor is needed. This design allows to tap into the benefits of the economy of scale and yields in the production at disruptive costs. At the same time, the sterile production conditions enable the product to free of contaminants. I house quality control assures matching concentrations needed for the end product.
This approach allows to use the economy of scale since the amount of manual labor stays constant even for a production run at > 50m3. Hereby, we are transferring bioprocess control and -optimization routines originating from the pharma industry to achieve high product quality.
AMF production at a disruptive price
Given the high effort necessary for mycorrhiza production correlated with conventional production approaches, the cost of goods for the production of mycorrhiza makes economically feasible pricing hardly possible.
In Virto - product quality
Moreover, we have been investing substantial effort in establishing novel methods of analysis in order to ensure product quality and quantity. This allows the application of the quality of design principles starting at lab-scale to ensure a high-performance product at an unrivaled low selling price.
Further products from Hairy roots
VALUABLE PLANT EXTRACTS – SECONDARY METABOLITES
Various active pharmaceutical ingredients (API) have been discovered in plants. Those ingredients are produced by the plant as secondary metabolites haven't used only as pharmaceuticals but also e.g. nutraceuticals, fragrance, or flavoring essence. Today, the less complex compounds are commonly produced by chemical synthesis (e.g. vanillin) or by microbial bioprocesses. However, the most complex ones are still sourced from the plant, even in the 21st Century. Hairy roots allow producing the relevant compounds as natural products using a bioreactor instead of vast areas of land.
While chemically simple compounds as e.g. flavors (vanillin) can be easily synthesized by the means of organic chemistry, more complex compounds are difficult to produce. Hairy roots offer direct access to complex compounds produced as secondary metabolites.