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Commercial Scale (commercial + scale)
Selected AbstractsMonoclonal antibodies: a morphing landscape for therapeuticsDRUG DEVELOPMENT RESEARCH, Issue 10 2006Nicholas C. Nicolaides Abstract The concept of using antibodies as therapeutics to cure human diseases was postulated nearly 100 years ago by Paul Ehrlich and subsequently enabled by the discovery of hybridoma technology by Kohler and Milstein in 1975. While the use of monoclonal antibodies (mAbs) as drugs that can specifically target a disease-associated antigen is compelling, it has taken a quarter century for these molecules to be adopted as bona fide therapeutic agents. Despite their slow pursuit in drug development during the pioneering years, it is now estimated that there are nearly 500 mAb-based therapies in development. Major factors that have influenced the acceptance of monoclonal antibodies as therapeutics include their drug safety profiles, technological advancements for facilitating mAb discovery and development, and market success. Early on, it was demonstrated that antibodies could elicit clinical benefit by antagonizing a specific antigen without the common side effects that are prevalent with small chemical entities due to their nonspecific effects on homeostatic biochemical pathways. In addition, the significant technological advances that the biotechnology industry has established for developing and producing monoclonal antibodies at commercial scale in a more efficient and cost-effective manner has broadly enabled their use as therapeutics. However, despite the beneficial pharmacologic advantages and technological advances, it has been the sheer market success that monoclonal antibody products have achieved over the past few years that has propelled their vast pursuit by the biopharmaceutical industry in light of their value-creating potential. Here we provide an overview of the monoclonal antibody industry and discuss evolving technologies and strategies that are being pursued to overcome challenges in the changing marketplace. Drug Dev. Res. 67:781,789, 2006. © 2007 Wiley-Liss, Inc. [source] Cost-Affordable Technique Involving Equal Channel Angular Pressing for the Manufacturing of Ultrafine Grained Sheets of an Al,Li,Mg,Sc Alloy,ADVANCED ENGINEERING MATERIALS, Issue 8 2010Rustam Kaibyshev A two-step process consisting of modified equal channel angular pressing (ECAP) and subsequent isothermal rolling (IR) was developed to produce thin sheets of aluminum alloys with ultra-fine grained (UFG) structure. Significant increase in the efficiency of ECAP was attained by using flat billets and a back pressure system. The incorporation of final IR into technologic route provides a reduced strain which is necessary to impose for the fabrication of thin sheets with UFG structure. In addition, it allows producing relatively "long billets." In order to demonstrate the feasibility of this technique an Al,5.1Mg,2.1Li,0.17Sc,0.08Zr (wt %) alloy was subjected to ECAP at 325,°C to a total strain of ,8 using processing route CX. The operation time of this processing did not exceed 15,min. Subsequent IR at the same temperature with a total reduction of 88% was applied to produce thin sheets with a 1.8,mm thickness and an average size of recrystallized grains of ,1.6,µm. These sheets exhibit extraordinary high superplastic ductilities. In addition, this material demonstrated almost isotropic mechanical behavior at room temperature. The maximum elongation-to-failure of ,2700% was attained at a temperature of 450,°C and an initial strain rate of 1.4,×,10,2 s,1. Thus it was demonstrated that the two-step processing consisting of ECAP with a back pressure followed by IR was a simple technique providing potential capability for the fabrication of superplastic sheets from an Al,Mg,Li,Sc alloy on a commercial scale. [source] Variability of Endotoxin Expression in Bt Transgenic CottonJOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 1 2007H. Z. Dong Abstract Transgenic cotton expressing Bt (Bacillus thuringiensis) toxins is currently cultivated on a large commercial scale in many countries, but observations have shown that it behaves variably in toxin efficacy against target insects under field conditions. Understanding of the temporal and spatial variation in efficacy and the resulting mechanisms is essential for cotton protection and production. In this review, we summarize current knowledge on variability in Bt cotton efficacy, in particular on the induced variability by environmental stresses. We also discuss the resulting mechanisms and the countermeasures for the inconsistence in efficacy in Bt cotton. It is indicated that insecticidal protein content in Bt cotton is variable with plant age, plant structure or under certain environmental stresses. Variability in Bt cotton efficacy against target insect pests is mainly attributed to the changes in Bt protein content, but physiological changes associated with the production of secondary compounds in plant tissues may also play an important role. Reduction of Bt protein content in late-season cotton could be due to the overexpression of Bt gene at earlier stages, which leads to gene regulation at post-transcription levels and consequently results in gene silencing at a later stage. Methylation of the promotor may be also involved in the declined expression of endotoxin proteins. As a part of total protein, the insecticidal protein in plant tissues changes its level through inhibited synthesis, degradation or translocation to developing plant parts, particularly under environmental stresses, thus being closely correlated to N metabolism. It can be concluded that developing new cotton varieties with more powerful resistance, applying certain plant growth regulators, enhancing intra-plant defensive capability, and maintenance of general health of the transgenic crop are important in realizing the full transgenic potential in Bt cotton. [source] Studies on bioemulsifier production by Acinetobacter strains isolated from healthy human skinJOURNAL OF APPLIED MICROBIOLOGY, Issue 2 2001J.R. Patil Aims: In recent years, interest has been growing in the search for novel bioemulsifiers. Many bacterial genera including Acinetobacter have been reported to produce bioemulsifiers. The present study aims to screen Acinetobacter isolates from healthy human skin for bioemulsifier production. Methods and Results: Acinetobacter junii SC14 produced maximum bioemulsifier in the presence of almond oil during stationary growth phase at 37°C and pH 7·2. Partially purified, nondialysable bioemulsifier from SC14 was a proteoglycan. The protein and polysaccharide fractions resulted in 95·2% reconstitution of the emulsification activity. The role of esterase in the release of cell-bound emulsifier and the contribution of capsular polysaccharide to the emulsification activity were observed. Conclusion:Acinetobacter strains from human skin exhibited better emulsification activity than that by burn wound or soil isolates, owing to the inherent differences in chemical microenvironment of their habitats. Significance and Impact of the Study: Investigation of skin commensals, especially acinetobacters, would lead to the discovery of novel bioemulsifiers with interesting properties. Attempts of screening and strain improvement directed towards skin commensals will open up new avenues for strains producing bioemulsifier on a commercial scale. [source] ROLE OF SATURATED FATTY ACIDS IN LIPASE PRODUCTION , USING PSEUDOMONAS AERUGINOSAJOURNAL OF FOOD BIOCHEMISTRY, Issue 6 2007A.N. SARAVANAN ABSTRACT Complex substrates always induce substantial amount of enzyme production during hydrolysis by microorganisms. In this study, ghee was taken for its saturated fatty acid content and analyzed as an inducer for the production of lipase. With ghee emulsion, the bacterium Pseudomonas aeruginosa at optimal condition produced 60 units/min/L at 72 h. With olive oil emulsion, this organism produced only 41 units/min/L as maximum at 96 h. The saturated fatty acids present in ghee make it a hard substance for hydrolysis, which is the reason for the increased enzyme production. This was evaluated by the iodine number experiment. Ghee can also reduce the production cost whereas the costlier olive oil constitutes 25,50% of the total production cost for a commercial scale. The experimental results showed that the saturated fatty acids play an important role in lipase enzyme induction by P. aeruginosa. The use of ghee is cost-effective; hence, it can be used as a potential inducer for lipase production. PRACTICAL APPLICATIONS Lipases are industrially very important enzymes. They are used in pharmaceutical, food, soap and other industries. In lipase production, olive oil is the main constituent. Comparatively, olive oil is costlier; hence, it increases the production cost of lipase. So, this study was done to replace olive oil with a much cheaper ghee using Pseudomonas aeruginosa. The ghee-containing medium gave a very good result because of the presence of complex saturated fatty acids. The ghee-containing medium produced 60 units/min/L at 72 h. The olive oil medium, which contains mainly unsaturated fatty acids, produced only 41 units/min/L as maximum at 96 h. Hence, in the commercial scale, ghee can reduce raw material cost as well as operation time cost significantly when it is used as substrate. [source] Effects of organic and conventional production systems on quality and nutritional parameters of processing tomatoesJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 2 2009Joy Rickman Pieper Abstract BACKGROUND: The impact of organic and conventional production systems on quality and nutritional parameters of fruits and vegetables is still under discussion. The objective of this study is to determine whether the production system has a significant effect on the quality and nutritional content of one variety of processing tomatoes grown on a commercial scale by comparing three different growers for two production years. RESULTS: Conventional tomatoes appeared to be more mature at time of harvest as determined by visual inspection of color. Total and soluble solids were significantly higher and consistency was greater in organic tomatoes. Differences in nutrient content were not statistically significant between production systems. Glutamate, glutamine, and tyrosine levels were significantly higher in conventional tomatoes, as were total nitrogen and ammonium concentrations. CONCLUSION: Results from this study show that nutritional and quality parameters vary greatly by grower, production system, and year for the same tomato cultivar. Significantly higher average soluble solids content and consistency in organic tomatoes are especially important to the processing tomato industry. The apparent slower development of organic tomatoes may be responsible for many of the significant findings in this study and may explain some of the conflicting reports in previous literature. Copyright © 2008 Society of Chemical Industry [source] Effects of Larval Stocking Density on Laboratory-Scale and Commercial-Scale Production of Summer Flounder Paraliehthys dentatusJOURNAL OF THE WORLD AQUACULTURE SOCIETY, Issue 3 2000Nicholas J. King Experiments 1 and 2 at commercial scale tested the densities of 10 and 60 larvae/L, and 10, 20, and 30/L, respectively. The laboratory scale experiment tested the densities of 10, 20, 30, and 40 larvae/L. Experiments were carried out in two separate filtered, flow-through seawater systems at URI Narragansett Bay Campus (laboratory-scale), and at GreatBay Aquafarms, Inc. (commercial-scale). At both locations, the larvae were raised in a "greenwater" culture environment, and fed rotifers and brine shrimp nauplii according to feeding regimes established for each location. Water temperature was maintained at 21C (± 2) and 19C (± 1) for the duration of laboratory and commercial experiments, respectively. Experiments 1 and 2 at the commercial location were terminated at 42 and 37 d post hatch (dph), respectively, and the laboratory experiment lasted 34 DPH. Larvae initially stocked at 10/L grew to an average length of 14.3 and 14.4 mm, and were significantly larger (P < 0.05) than those stocked at 30/L (13.1 mm) and 60/L (11.7 mm) in commercial scale experiments I and 2, respectively. At laboratory scale, no significant differences in length were detected, although mean total length tended to decrease with increasing stocking density (average length of 14.2, 13.3, 12.7, and 12.7 mm for treatments of 10, 20, 30, and 40/L, respectively). Final survival percentage was not affected by stocking density in either commercial experiment, and was 61 and 40% for treatments of 10 and 60/L in Experiment 1, respectively, and 62, 59, and 56% for Experiment 2, respectively. Similarly, there was no significant difference in final survival percentage among treatments in the laboratory experiment, which averaged 59, 55, 56, and 37% for treatments of 10, 20, 30, and 40L. respectively. Since larval length was not different between the intermediate densities (20 and 30 Iarvae/L), and because high-density rearing can produce a much greater numerical yield per tank, we recommend a density of 30 larvaen as an optimal stocking density for the hatchery production of summer flounder. [source] (203) Manufacturing Process for a Highly Purified, Stable Liquid Formulation of Botulinum Toxin Type B (MyoblocÔ)PAIN MEDICINE, Issue 3 2001Andrew Grethlein Botulinum toxin type B (BoNT-B; MyoblocÔ) is a new botulinum toxin with demonstrated efficacy in patients with cervical dystonia, and has been found to decrease neck pain associated with this disorder. Developmental work has led to the commercial-scale production of a uniform, highly purified toxin complex in a liquid formulation. Production of BoNT-B involves fermentation, recovery and purification from Clostridium botulinum. The reliability and robustness of the process were tested by altering critical process parameters (eg, pH, temperature) and showing that a high-quality product resulted even in conditions detrimental to C botulinum fermentation. Consistency and key quality attributes (purity, complex integrity, percent nicking, specific activity) of the toxin were assessed using a series of biochemical tests, which were validated as precise and accurate and are now routinely used in quality control analysis. Results confirmed production of an intact, uniform toxin complex with consistent purity, percentage nicking (a measure of toxin activation) of over 70%, and specific activity over 90 U/ng in three manufacturing runs. BoNT-B is manufactured as a slightly acidic liquid formulation that maintains complex integrity, reducing the potential for generating neutralizing antibodies. The potency of drug substance, dilute bulk solution, and finished product was shown to be reliable using the validated mouse intraperitoneal LD50 potency assay. The liquid formulation of BoNT-B was found to be stable for at least 9 months at 25°C and at least 3 years at 2,8°C. BoNT-B has a long shelf-life and may be produced on a commercial scale reliably and reproducibly, making it readily available and convenient to store and use. Support of Elan Pharmaceuticals is gratefully acknowledged. [source] Preface: phys. stat. sol. (b) 245/3PHYSICA STATUS SOLIDI (B) BASIC SOLID STATE PHYSICS, Issue 3 2008Christopher W. Smith This is the third Special Issue of physica status solidi (b) focusing on materials with a negative Poisson's ratio or other ,anomalous' physical properties. This issue contains selected papers from the First International Conference on Auxetics and Anomalous Systems held at the University of Exeter, UK, on 4,6 September 2006. Around 50 participants from all over the world as well as from a wide range of scientific and engineering disciplines contributed to what was a highly successful conference. This conference follows in the footsteps of two previous workshops held at the Mathematical Research and Conference Centre in B,dlewo near Pozna,, Poland, in 2004 and 2005 [1, 2]. The papers selected for this issue publish recent results obtained for ,anomalous systems' in experiment, theory and computer simulations. In the following we summarize very briefly their contents. Alderson and Coenen compare the performance of auxetic composites to similar systems with conventional positive Poisson's ratios. They find that there are indeed differences which appear to arise from the change of the overall Poisson's ratio of the composite, some beneficial like a rise in impact tolerance at low impact rates, and others deleterious such as the reduced tolerance at higher impact rates. This is one of the first investigations of possible applications for auxetic materials. The two papers by Gaspar and Koenders both examine the effects of disorder upon anomalous properties, especially negative Poisson's ratio. In the first one Gaspar demonstrates how a mean strain estimate fails to predict negative values of Poisson's ratio because of an inability to account for local fluctuations in elastic properties. For instance it is shown that the volume fraction of auxetic regions in an globally auxetic material (measured experimentally) are smaller than a mean strain homogenisation would require. Koenders and Gaspar explore the elastic properties, and especially Poisson's ratio, of a heterogeneous 2D network of bending beams. They predict auxetic behaviour arising from localised disorder in the packing, and therefore effective locally aggregated elastic properties of the beams. In the three articles by Gatt et al. and Grima et al. models based on simple geometry are used to explain the behaviour of seemingly disparate systems, i.e. 2D honeycombs systems and zeolite SiO2 networks. Two papers concerning honeycombs demonstrate relationships between elastic properties and structure and the bounds for auxetic behaviour. The paper concerning the zeolite Natrolite uses numerical force field based energy minimisation methods to simulate the response of this particular zeolite to applied forces and then simplifies the predicted properties even further by considering structural units as rigid 2D polyhedra linked by flexible hinges. In a similar vein, though using a different approach and concerning a very different form of matter, Heyes shows how the heterogeneity in an assembly of particles in a liquid can affect the elastic properties of a liquid and notably the infinite frequency Poisson's ratio. Heyes uses the Molecular Dynamics approach to simulate a Lennard,Jones fluid under various pressures, notably comparing behaviour under positive and negative pressures. In their first paper Jasiukiewicz and co-authors derive elastic constants of 2D crystals for all four classes of 2D crystalline solids: hexagonal (isotropic), quadratic, rectangular, and oblique systems. In their second paper they demonstrate conditions required for auxetic behaviour of 2D crystals. Auxetic solids are further divided into those with some negative Poisson's ratios (auxetic), all negative Poisson's ratios (completely auxetic) and no negative Poisson's ratios (non-auxetic). Lakes and Wojciechowski consider counterintuitive properties of matter, like negative compressibility, negative Poisson's ratio, negative thermal expansion, negative specific heat, and negative pressure. They present and interpret experimental observations of negative bulk modulus in pre-strained foams. They propose also a constrained microscopic model which exhibits negative compressibility. Finally, they solve a very simple thermodynamic model with negative thermal expansion. Martin et al. take a long stride toward a real world application of auxetic materials with a wide ranging study starting with numerical modelling of a wingbox section to experimental testing in a wind tunnel. They show that an auxetic core in a wing box section can allow a passive aero-elastic response which can be tailored by careful design of the core so that camber, and thus drag, is reduced with increasing airspeed but without sacrificing structural integrity. Miller et al. consider another anomalous physical property, negative thermal expansivity, and its application in the form of particulate composites for amelioration of stresses arising from thermal mismatch. They show via experiments that particles with a negative coefficient of thermal expansion may be used as a composite reinforcer to reduce overall thermal expansion and behave according to the standard volume fraction based models. Narojczyk and Wojciechowski examine the effects of disorder upon the bulk elastic properties of 3D fcc soft sphere systems in terms of particle size. Systems, such as colloids, can be thought of in such terms. The study shows that higher order moments of probability distribution do not influence the bulk elastic properties much, but that lower moments such as the standard deviation of particle size influence the elastic properties greatly. The "hardness" of the particle interaction potential is also important in this context. In general, it is shown that the effect of increasing polydispersity is to increase the Poisson's ratio, except the [110] [10] directions. Scarpa and Malischewsky in their paper on Rayleigh waves in auxetic materials show how the Rayleigh wave speed is affected by the Poisson's ratio. The behaviour is complex and depends upon the homogeneity within the material, for instance slowing with decreasing Poisson's ratio in isotropic solids, but showing the reverse trend and increased sensitivity to Poisson's ratio in laminate composites. Scarpa et al. explore the buckling behaviour of auxetic tubes via three types of model, a simple beam mechanics and Eulerian buckling model, a 3D linear elastic FE model and a bespoke non-linear continuum model. The more sophisticated models provide increasing insight into the buckling behaviour though the simple beam model predicts reasonably well in the pre-buckling linear region. Some unexpected and interesting behaviour is predicted by the continuum model as the Poisson's ratio approaches the isotropic limit of ,1, including increasing sensitivity to Poisson's ratio and rapid mode jumping between integer wave numbers. The paper by Shilko et al. presents an analysis of a particular kind of friction joint, a double lap joint, and explores the effects of altering the elastic properties of one component, in particular it's Poisson's ratio. The manuscript introduces the evolution of smart materials from monolithic materials, and the classification of composites exhibiting negative Poisson's ratios. The paper then presents the case of a double lap joint and performs a sensitivity type study, via a 2D FE model, of the effects of changing the elastic properties and degree of anisotropy of one section of the model on various parameters defining the limits of functionality of the joint. The main finding is that an enhanced shear modulus, via a negative Poisson's ratio, can endow such a friction joint with superior performance. Manufacturing of auxetic materials on a commercial scale has proved to be the largest obstacle to their fuller exploitation. The paper by Simkins et al. explores one route for post processing of auxetic polymers fibres produced by a conventional melt extrusion route. Simkins et al. showed that a post process thermal annealing treatment, with carefully optimised parameters, was able to even out otherwise inhomogenous auxetic properties, and moreover improve other elastic and fracture properties often sacrificed for auxetic behaviour. We gratefully acknowledge the support given by the sponsors of the conference, namely the EPSRC of the UK and Auxetic Technologies Ltd. (UK). We also thank the Scientific Committee, the Organising Committee, and all the participants of the conference. (© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Prospects for molecular breeding of barleyANNALS OF APPLIED BIOLOGY, Issue 1 2003W T B THOMAS Summary Data from UK Recommended List Trials showed that the introduction of new cultivars of spring and winter barley has maintained a significant increase in yield over time, whereas there has been no significant improvement in hot water extract, the major determinant of good malting quality, in either crop. Commercial barley breeding is based upon phenotypic selection, and the introduction of molecular breeding methods must either increase the rate of advance, or offer an improvement in the cost-effectiveness of breeding programmes. Molecular breeding can be applied to either single gene or polygenic characters but is not widely used in commercial barley breeding, other than as a marker for resistance to the Barley Yellow Mosaic Virus complex. There are many reports of potential targets for use in molecular breeding but the few validation studies that have been carried out to date are disappointing. Results from genomics studies are likely to lead to the identification of key candidate genes, which can be associated with economically important characters through co-location on certain chromosomal regions. Associations between candidate gene sequence haplotypes and phenotypic characteristics is expected to identify allelic combinations, which are most frequently observed in successful cultivars, that can be used in molecular breeding of barley on a commercial scale. [source] An analysis of variability in the manufacturing of dexosomes: Implications for development of an autologous therapy,BIOTECHNOLOGY & BIOENGINEERING, Issue 2 2005Sanjay Patel Abstract Dexosomes are nanometer-size vesicles released by dendritic-cells, possessing much of the cellular machinery required to stimulate an immune response (i.e. MHC Class I and II). The ability of patient-derived dexosomes loaded with tumor antigens to elicit anti-tumor activity is currently being evaluated in clinical trials. Unlike conventional biologics, where variability between lots of product arises mostly from the manufacturing process, an autologous product has inherent variability in the starting material due to heterogeneity in the human population. In an effort to assess the variability arising from the dexosome manufacturing process versus the human starting material, 144 dexosome preparations from normal donors (111) and cancer patients (33) from two Phase I clinical trials were analyzed. A large variability in the quantity of dexosomes (measured as the number of MHC Class II molecules) produced between individual lots was observed (,>,50-fold). An analysis of intra-lot variability shows that the manufacturing process introduces relatively little of this variability. To identify the source(s) of variability arising from the human starting material, distributions of the key parameters involved in dexosome production were established, and a model created. Computer simulations using this model were performed, and compared to the actual data observed. The main conclusion from these simulations is that the number of cells collected per individual and the productivity of these cells of are the principal sources of variability in the production of Class II. The approach described here can be extended to other autologous therapies in general to evaluate control of manufacturing processes. Moreover, this analysis of process variability is directly applicable to production at a commercial scale, since the large scale manufacture of autologous products entails an exact process replication rather than scale-up in volume, as is the case with traditional drugs or biologics. © 2005 Wiley Periodicals, Inc. [source] | |||||||||||||||||||