Day 1 :
French-German Research Institute of Saint-Louis, France
Keynote: Spray flash evaporation for the continuous production of high performance nanodrugs: New challenges for a new disruptive process
Time : 09:30-10:15
Denis Spitzer received his PhD in Physical Chemistry in 1993 at University Louis Pasteur of Strasbourg. He is the founding and current Director of the NS3E Research Laboratory UMR 3208 ISL/CNRS/UNISTRA. He conducts research in continuous nano-crystallization processes of organic nanomaterials such as model medicaments and energetic materials. He is the inventor of the SFE process. He is the author of more than 150 publications and scientific reports.
NS3E laboratory developed the Spray Flash Evaporation (SFE) for preparing drug nanoparticles at industrial scale. The process was several times patented up to now. The solution is kept in a pressurized tank separated from a vacuum chamber by a hollow cone nozzle, used both to heat and spray the liquid. The instantaneous evaporation of the solvent originates from the combination of the abrupt pressure drop and the high energy stored by the overheated solvent prior to nebulisation. The flash evaporation leads to small crystallites with narrow size distribution. The nanoparticles may be composed of single compounds, mixtures of several substances or co-crystals. In the domain of medicaments, co-crystals are of critical importance as they enhance bioavailability and up-take by the human body of Active Pharmaceutical Ingredients (API). Up to now, most used techniques are of batch nature and are not able to give access in big amounts to nano-sized crystals or co-crystals of therapeutic interest. The SFE permits the continuous manufacturing of nano-sized co-crystals, in large amounts with a kinetic complying with the pharmaceutical industry’s requirements. The efficiency of SFE is shown by the manufacturing of pure nano-medicaments but also of nano-co-crystals such as resveratrol/4-aminobenzamide (1/1), caffeine/oxalic acid (2/1) and caffeine/glutaric acid (1/1), with a mean particle size of between 30 and 100 nm. After showing the possibility to continuously nano-crystallize medicaments, the presentation will focus on different main challenges to further enhance the production capacity and also to understand the SFE process itself. Among different techniques and metrologies used or specially developed such as phase Doppler interferometry (Figure) and AFM-TERS spectroscopies, the presentation will also focus on different crystallization configurations used.
Arkansas State University, USA Infinite Enzymes, LLC, USA
Time : 10:15-11:00
Elizabeth E Hood has 35 years of experience in Biology. She is Distinguished Professor of Agriculture at Arkansas State University and; CEO of two biotechnology start-up companies—Infinite Enzymes, LLC and Infinite Eversole Strategic Crop Services, LLC. Previously, she was an Associate Vice Chancellor for Research and Technology Transfer at ASU; Program Director in Molecular and Cellular Biosciences at the National Science Foundation: Leader in forming one of the world’s foremost transgenic plant research groups at ProdiGene, a plant biotechnology company. She has completed her PhD in Plant Biology at Washington University and MS in Botany awarded by Oklahoma State University
Industrial enzymes are excellent technologies to apply in manufacturing to alleviate environmental pollution. Using plant-based materials allows manufacturing of goods from renewable resources. My laboratory and company are engaged in producing enzymes for industrial applications using the plant seed system. The advantages of the seed system are that the production costs can be quite low because scaling-up just involves planting more acres, the seed can be stored for years, and the enzymes are extremely stable in the seed. We use maize grain to express enzyme genes from fungal and bacterial sources that have specific applications in biofuels, bioproducts and waste water remediation. Genes for these enzymes are partially codon optimized and their expression is driven by either an embryo or an endosperm promoter and targeted to one of three subcellular locations—the cell wall, the endoplasmic reticulum or the vacuole. Expressed enzymes include three cellulases, a phospholipase, a Mn peroxidase, and a laccase. Once the gene is expressed and a high-expressing event chosen, breeding into elite inbred germplasm commences. Applications of the various enzymes will be discussed along with regulatory considerations
BioEnergy Society of Singapore, Singapore. Ngee Ann Polytechnic, Singapore
Anli Geng is currently the Assistant Director of Life Sciences and Chemical Technology of Ngee Ann Polytechnic. She currently holds the President position at BioEnergy Society of Singapore (BESS) and she is also the Co-founder and Director of Sunvisiae Biotech Pte Ltd, a Singapore-based industrial biotechnology company. Prior to joining Ngee Ann Polytechnic, she was working at Institute of Environmental Science and Engineering (IESE) as a Research Scientist. She has more than 25 years of R&D experience, working extensively on environmental biotechnology, green energy technology and industrial biotechnology. She has more than 30 journal publications and her work has been presented in many international conferences. Her current research focus at Ngee Ann Polytechnic is developing novel microorganisms to produce industrial enzymes, chemicals and fuels, novel nutraceuticals and cosmetics ingredients. She obtained Ngee Ann Polytechnic Staff Excellence Award and IChemE Award on Sustainable Technology in 2012.
Industrial biotechnology is a set of practices that use living cells (such as bacteria, yeast, algae) or component of cells like enzymes, to generate industrial products and processes. This presentation focuses on the application of industrial biotechnology in technology development for fuel and chemical production. The talk will cover industrial biotechnology application in the development of cellulolytic enzymes and metabolic engineering of yeast for the conversion of lignocellulosic biomass to fuels and chemicals. The conversion of oil palm empty fruit bunch, the main biomass resource in Southeast Asia, will be particularly discussed.
- Environmental Biotechnology | Industrial and Microbial Biotechnology |Plant and Agriculture Biotechnology
University of Haifa, Israel
Elizabeth E. Hood
Arkansas State University, USA
Mark Nuijten trained as a Physician and worked in clinical practice before completing an international MBA from Erasmus University, Rotterdam. He completed his PhD in Health Economics at the Erasmus University, Rotterdam, in 2003 and the thesis entitled as “In search of more confidence in health economic modeling”. He was Board Director of ISPOR (2002-2004) and Chair of the Management Board of Value in Health (2002-2004). He is a pioneer in the field of Healthcare Innovation in Biotechnology and Nutrition, and has been the first classical health economist successfully applying and developing sales forecast methodologies for valuation of biotechnology companies. Prior to setting up A2M, he was a partner with MEDTAP International. As a VP Business Development for Europe, he established global Pricing and Reimbursement Consultancy Services for MEDTAP. Before MEDTAP, he was a Managing Director of the Quintiles office in the Netherlands
Registration of a medicinal product by EMA or FDA used to be the main determinant for the future sales forecast of the product and would justify a higher valuation of the share of the company, especially for a biotech company with only a limited number of products. Contrary, new emerging requirements for reimbursement authorities, payers and drug policy changes are increasingly going to determine the actual future sales and the actual post-launch costs. The current most important criteria for coverage decisions are effectiveness, cost-effectiveness and budgetary impact, which are taken into consideration to make a value for money decision. As the future financial performance of a pharmaceutical company is directly related to the free cash flow of a new drug, an appropriate assessment of the potential sales forecast of a portfolio of forthcoming new drugs is an important predictor of the economic value of a pharmaceutical company. Today, such an assessment should include the estimated effects of the new emerging requirements for reimbursement authorities, payers and the effects of other pharma policy changes, as pay-for-performance based financial agreements.
Objective: This presentation aims to provide a strategic value scan for biotechnology products at the early onset of the development program considering the emerging hurdles for market access. The application of the early phase scan will be based on a hypothetical new innovative drug in breast cancer.
Methods: The outcomes of the strategic value scan are determined by the key decision criteria: efficacy and safety, cost-effectiveness, budget impact and additional criteria may be included depending on the disease area. The input of the strategic scan is based on a sales forecast model, a cost-effectiveness model, and a pricing model, which are interacted and executed simultaneously. The strategic value scan will provide guidance on the position of the new product in the treatment pattern for each scenario and the expected comparators in each position. The cost-effectiveness model and pricing model will provide upper limits for the pricing potential for each scenario and the expected comparators in each position. These outcomes can be linked with a discounted cash flow model to optimize the economic value of the biotechnology company taken into considerations the hurdles for reimbursement and market access. The value scan includes various scenarios (e.g. negative, base case and optimistic) for the expected clinical profile of the new product and the positioning of the new product in the treatment pattern (e.g. 1-line, 2-line, 3-line treatment). It is important to predict the incremental benefit of the new product versus the relevant expected comparators at each possible position. Changes in design of the forthcoming clinical trial or positioning of the new product may increase the economic value of the company. For example, health economic data (effectiveness and resource utilisation) may be collected alongside the forthcoming clinical trial, which may be used as input for the health economic models.
Conclusion: We present a novel approach for the early phase valuation of biotechnology products from a broader perspective by bridging concepts from health economics, market access, pricing and the economics of business economic valuation
Agricultural University of Kraków, Poland
Tomasz Warzecha has completed his PhD in 2001 from Agricultural University in Kraków, Poland. He has participated at the International Postgraduate Course on Biotechnology in Agriculture, Plants and Microorganisms at the Hebrew University of Jerusalem. Additionally completed the Pedagogical Studium, majored in Biology and Chemistry at Jagiellonian University in Krakow, Poland. He has worked in a project focused to examine natural variation in the recombination pathways in maize at the Department of Plant Breeding and Genetics at Cornell University, Ithaca, USA.
One of the most effective ways to generate oat DH lines is to perform a wide crossing with maize. An elevated level of homozygosity possessed by DH lines is a feature desirable for the durability of certain characteristics of new autogamous cultivars. Unlike other cereals, oat can form stable and fertile partial hybrids after pollinating with maize, since oat is able to retain one or more maize chromosomes without a lethal effect. The identification of an oat-maize addition lines could help in the selection of partial hybrids and describing the impact of additional chromosomes on the morphological and agricultural features of oat. The aim of the study was to detect maize DNA introgression into the oat genome using the PCR technique. To establish whether maize genomic DNA was present in oat DH lines, a fragment of maize-specific retro-transposon Grande1 (500 bp) was amplified and was detected after an electrophoresis in an agarose gel. All DH lines with detected fragments of retro-transposon Grande1 were analyzed with genomic in situ hybridization to detect and visualize maize chromosomes. Among the 94 oat DH lines that were obtained, 47 retained the maize chromatin, as inferred from the presence of a fragment of the Grande1 retro-transposon. Fertile lines that produced grains underwent GISH analysis, which revealed from 1 to 4 maize additional chromosomes. Aside from whole maize chromosomes, a banding pattern was also observed in most cases, which presumably co-localized with 25S rDNA sites. Additional hybridization signals were detected in 2-3 chromosome pairs depending on the analyzed line. These signals might correspond to oat’s 5S rDNA sites, although it cannot be eliminated that these sequences originated from the maize genome and were inserted into oat chromosomes.
Queensland University of Technology, Australia
Felipe Gonzalez is an Associate Professor in the Science and Engineering Faculty, Australia and team Leader for Integrated Intelligent Airborne Sensing Laboratory at the Queensland University of Technology, Australia. He holds a BE (Mech) and a PhD from the University of Sydney. His research explores bioinspired optimization, uncertainty based UAV path planning and UAVs for environmental monitoring. He leads the CRC plant biosecurity project evaluating unmanned aerial systems for deployment in plant biosecurity and the CRC PB 2135 optimizing surveillance protocols using unmanned aerial systems and developing pest risk models of buffel grass using unmanned aerial systems and statistical methods. He is a Chartered Professional Engineer and member of Professional Organizations including the RAeS, IEEE and AIAA.
The use of unmanned aerial vehicles (UAVS) or drones in agriculture and plant biosecurity is rapidly increasing. Grape phylloxera (Daktulsphaira vitifoliae Fitch) is a serious economically important invasive insect pest of European grapevine (Vitis vinifera L). Although widely present in most grape-growing countries worldwide, its distribution within Australia is limited, mainly due to strict biosecurity measures in place at farm, regional and state levels. As the insect is very small, and primarily lives underground on the roots of the grapevines, it is very hard to detect until the symptoms of infestation appear (slow stunted growth and premature yellowing of leaves), usually after 2-3 years (although in some instances this can be longer). This research, part of a Plant Biosecurity CRC project on “Optimising plant biosecurity surveillance protocols for remote sensing using unmanned aerial systems”, evaluates the use of UAV based high resolution RBG, thermal, multi- and hyper-spectral imagery at detecting symptoms of phylloxera infestation at two different vineyards, multi-variety grapevines, at two separate time periods and under different levels of phylloxera infestation. Early detection of phylloxera within the first year would allow vineyard managers to implement phytosanitary measures to restrict or slow the spread of the pest and reduce future costs and losses in production. Previous research indicated that early infection of grapevines by phylloxera can be detected with hand-held spectro-radiometers and changes in leaf and canopy level reflectance were associated with changes in leaf chemistry. Datasets from each imagery type are compared to existing phylloxera detection practices; visual inspection, ground-based insect traps, soil DNA probes as well as being overlain with EM38 ground conductivity survey data. The ultimate aim of this study is to move towards a more targeted integrated approach for phylloxera detection and is the first study of its type to focus on a soil borne pest of biosecurity significance.
Great Lakes Forestry Centre, Canada
Guoxing Quan received his PhD degree in 1998 from Tokyo University of Agriculture and Technology, Japan. He worked as a Postdoctoral Fellow in Japan and Canada for several years. Currently, he is a Research Scientist working at Great Lakes Forestry Centre, Sault Ste. Marie, Ontario. He has published more than 20 papers and been a reviewer for many scientific journals. He has worked on transgenic silkworm, RNAi and owns three patents. His current research focuses on the identification of genes involved in adapting to unfavorable environmental conditions and how the changing climate affects insect distribution and outbreaks
Small heat shock proteins are a superfamily of molecular chaperones and are characterized by the presence of a conserved α-crystallin domain. They exhibit ATP-independent chaperone-like activity by assisting in the correct folding of nascent and stress-accumulated misfolded protein to prevent irreversible protein aggregation. Unlike HSPs of large molecular weight, the sHSPs display structural and functional diversity among different insect species. Some sHSPs may contribute to stress tolerance, enhancing insect survival in severe environmental conditions. As such, studying SHSPs may lead to a better understanding of how pest insect survives in unfavorable environments and how the changing climate affects their distribution and outbreaks. The spruce budworm, C. fumiferana is a destructive native forest defoliator in North America. In the past few hundred years, periodic outbreaks are known to have occurred across tens of millions of square kilometers of forest. Here, we report the identification of 15 sHSP genes from the spruce budworm transcriptome. Examination of the mRNA expression profiles of the sHSPs revealed that the levels varied according to the developmental stage and tissue as well as whether the insects were reared under normal and stress conditions. Nine sHSP genes were sensitive to heat shock stress. Some, but not all, sHSPs may play a vital role during diapause.
M Cristina Diez has completed her PhD in 1993 at Universidad Estadual de Campinas, Brazil. She is a Professor in Chemical Engineering Department and, the Director of Biotechnological Research Center Applied to the Environment (CIBAMA-BIOREN) of La Frontera University. She has published more than 115 papers in reputed journals. She is a member of FONDECYT's technology board. She is serving as an Editorial Board Member of the Journal of Soil Science and Plant Nutrition.
Bio-purification system is used to adsorb and degrade pesticide spills during handling of products before its application. The PBS has an organic matrix (biomix) composed of soil, commercial peat and wheat straw (1:1:2). We evaluated the adsorption capacity of different agro-industrial and lignocellulosic residues, as components of the biomix of the BPS, to treat water contaminated with pesticides. Sawdust, barley husk, compost and biochar were used in this process. Each biomix and individual components were characterized, and biomixes were formulated with partial replacement of 50% wheat straw or peat, moistened at 60-70% water holding capacity (WHC) and pre-incubated for 30 days at 20-25 °C. For kinetic studies, biomixes were contaminated with atrazine (ATZ), chlorpyrifos (CHL) and iprodione (IPR) at a concentration of 5 mg/L and to attain ionic strength, 0.01 M CaCl2 was added to it. Adsorption at 30, 60, 300, 600, 1080 and 1140 min of incubation at 22 ± 1 °C was evaluated. The adsorption isotherms were carried out with different amounts of biomix and concentration of pesticides for 24 hrs. It was observed that the highest adsorption capacity was achieved in biochar based biomixes, independent of the type of pesticide. CHL presents the highest adsorption rate, ATZ presents a constant and linear saturation for other biomezclas not presenting greater difference, and IPR differs its adsorption for each particular biomix. The Freundlich and Langmuir models were used to describe the kinetics of the adsorption process in the biomixes.
BioEnergy Society of Singapore, Singapore
Anli Geng is currently an Assistant Director of Life Sciences and Chemical Technology of Ngee Ann Polytechnic. She currently holds the President position in BioEnergy Society of Singapore (BESS). She is also the Co-founder and Director of Sunvisiae Biotech Pte Ltd, a Singapore-based industrial biotechnology company. Prior to joining Ngee Ann Polytechnic, she was working at Institute of Environmental Science and Engineering (IESE) as a Research Scientist. She has more than 25 years of R&D experience, working extensively in environmental biotechnology, green energy technology and industrial biotechnology. She has more than 30 journal publications and her work has been presented in many international conferences. Her current research focuses on developing novel microorganisms to produce industrial enzymes, chemicals and fuels, novel nutraceuticals and cosmetics ingredients at Ngee Ann Polytechnic. She obtained Ngee Ann Polytechnic Staff Excellence Award and IChemE Award on Sustainable Technology in 2012.
Talaromyces pinophilus UTA1 and EMM are cellulase hyper-producing mutants that originated from T. pinophilus OPC4-1 through UV irradiation and chemical mutagenesis by NTG and EMS. Full genome sequencing of these two mutants and the parent strain was conducted and 73 genes were identified with either SNPs or InDels. Functions of the 73 genes were identified using NCBI GenBank database. Among the 73 genes, 3 transcription factors were identified. They might be responsible for the enhancement of cellulase activity in mutant strains, UTA1 and EMM. Genes encoding the 3 transcription factors were successfully cloned to further confirm their enhancement in cellulase and hemicellulase production in mutant strains. Further genetic engineering of the mutant strain EMM was conducted to further enhance its enzyme production. A uracil auxotroph strain T. pinophilus EMU was isolated through random mutagenesis. A wild-type pyrF gene encoding orotate phosphoribosyl transferase (OPRTase, EC 18.104.22.168) isolated from T. pinophilus OPC4-1, the parent strain can be used as the selection marker for genetic engineering of strain T. pinophilus EMM. A marker recycle system was developed and was used for the knock-out of creA gene, the gene mediating catabolite repression. A creA gene knock-out strain, A creA 21 was successfully isolated. It demonstrated enhanced cellulase and xylanase production and higher resistance to the increased glucose concentration. The genetic engineering tools were successfully developed for strain T. pinophilus EMM and disruption of creA gene in strain EMM was effective for enhanced enzyme production.