Production Scale (production + scale)

Distribution by Scientific Domains

Selected Abstracts

Nanofiltration of plasma-derived biopharmaceutical products

HAEMOPHILIA, Issue 1 2003
T. Burnouf
Summary. This review presents the current status on the use and benefits of viral removal filtration systems , known as nanofiltration , in the manufacture of plasma-derived coagulation factor concentrates and other biopharmaceutical products from human blood origin. Nanofiltration of plasma products has been implemented at a production scale in the early 1990s to improve margin of viral safety, as a complement to the viral reduction treatments, such as solvent,detergent and heat treatments, already applied for the inactivation of human immunodeficiency virus, hepatitis B and hepatitis C virus. The main reason for the introduction of nanofiltration was the need to improve product safety against non-enveloped viruses and to provide a possible safeguard against new infectious agents potentially entering the human plasma pool. Nanofiltration has gained quick acceptance as it is a relatively simple manufacturing step that consists in filtering protein solution through membranes of a very small pore size (typically 15,40 nm) under conditions that retain viruses by a mechanism largely based on size exclusion. Recent large-scale experience throughout the world has now established that nanofiltration is a robust and reliable viral reduction technique that can be applied to essentially all plasma products. Many of the licensed plasma products are currently nanofiltered. The technology has major advantages as it is flexible and it may combine efficient and largely predictable removal of more than 4 to 6 logs of a wide range of viruses, with an absence of denaturing effect on plasma proteins. Compared with other viral reduction means, nanofiltration may be the only method to date permitting efficient removal of enveloped and non-enveloped viruses under conditions where 90,95% of protein activity is recovered. New data indicate that nanofiltration may also remove prions, opening new perspectives in the development and interest of this technique. Nanofiltration is increasingly becoming a routine step in the manufacture of biopharmaceutical products. [source]

Control of the morphology and the size of complex coacervate microcapsules during scale-up

AICHE JOURNAL, Issue 6 2009
C. Y. G. Lemetter
Abstract Scale-up of complex coacervation, a fat encapsulation technology, is not trivial since the microcapsules morphology and size are highly affected by the processing conditions. So far it has been achieved empirically (trial and error approach). The goal of this study was to produce at various scale capsules with a single-oil droplet as the core material and small enough to be below sensory threshold. The turbulence level was identified as the main scale-up criterium and a master-curve could be drafted showing the capsule mean diameter as function of the Reynolds number, independent of the level of production scale. From a parent emulsion with specific oil droplets size (12,15 ,m), the Reynolds number had to be maintained above a critical value (15,000) to avoid capsules agglomeration with multiple oil cores and large particle sizes. To avoid aggregation, this turbulence level had to be kept until the temperature dropped below a critical value (14°C for a cooling rate of 35°C/2 h). Applying these learning led to a successful scale-up from bench (2 L) to a pilot plant scale of 50 L. © 2009 American Institute of Chemical Engineers AIChE J, 2009 [source]

Commercial-scale Validation of Temperature-step Rearing on Growth Physiology in Turbot, Scophthalmus maximus

Albert K. Imsland
The aim of this study was to investigate the possible benefit of "temperature-steps" (T-steps) rearing for juvenile turbot (initial weight 15.1 g) under realistic production scale and to determine whether initial growth advantage is maintained throughout the rearing period to market size. One group (called T-step 22-19-16) of juvenile turbot was reared at three different temperatures, that is, 22 C (from 17 to 60 g) followed by 19 C (from 60 to 100 g) and 16 C (>100 g); another group (called T-step 19-16) at two temperatures, that is, 19 C (from 17 to 100 g) and lowered to 16 C (>100 g); and the third group (called C16) at one constant temperature, that is, 16 C. Relative growth was significantly higher in the two T-step groups, with the T-step 19-16 showing the highest overall growth. Feed conversion efficiency was highest in the 19-16 group. Only minor effects of the experimental rearing on blood physiology were found, with one notable exception of inverse relationship between plasma glucose and growth. Overall, these findings indicate that a short interval of rearing fish at high temperature during the early juvenile phase may have a long-term effect on biomass increment in turbot. This is an important finding for the turbot industry. [source]

Effects of feeding and induction strategy on the production of BmR1 antigen in recombinant E. coli

A. Norsyahida
Abstract Aim:, To investigate the effects of feeding and induction strategies on the production of BmR1 recombinant antigen. Methods and Results:, Fed-batch fermentation was studied with respect to the specific growth rate and mode of induction to assess the growth potential of the bacteria in a bioreactor and to produce high yield of BmR1 recombinant antigen. Cells were grown at a controlled specific growth rate (,set) during pre-induction, followed by constant feeding postinduction. The highest biomass (24·3 g l,1) was obtained during fed-batch process operated at ,set of 0·15 h,1, whereby lower ,set (0·075 h,1) gave the highest protein production (9·82 mg l,1). The yield of BmR1 was increased by 1·2-fold upon induction with 1 mmol l,1 IPTG (isopropyl-,- d -thiogalactoside) compared to using 5 mmol l,1 and showed a further 3·5-fold increase when the culture was induced twice at the late log phase. Conclusions:, Combination of feeding at a lower ,set and twice induction with 1 mmol l,1 IPTG yielded the best result of all variables tested, promising an improved method for BmR1 production. Significance and Impact of the Study:, This method can be used to increase the production scale of the BmR1 recombinant antigen to meet the increasing demand for Brugia RapidÔ, a commercial diagnostic test for detection of brugian filariasis. [source]

Techne versus Technoscience: Divergent (and Ambiguous) Notions of Food "Quality" in the French Debate over GM Crops

In the French debate over genetically modified organisms (GMOs), actors present divergent definitions of food quality located between poles of technoscience and techne. Although scientists often define food quality in terms of technoscience, assessing food safety, small farmers often appeal to technes of production, positing GMOs as a rupture with artisanal culture. Whereas small farmers (from the union the Confédération Paysanne [CP]) deploy notions of "techne" to promote their anti-GMO campaign, they often define quality in an ambiguous way, vacillating between ideas of agricultural method (technique) or production scale. Despite this ambiguity, the CP successfully designates GMOs as la malbouffe, or "bad" food, establishing themselves as protectors of artisanal technés such as Roquefort. Finally, unlike many cultures that cast GMOs as "unnatural," the CP tends to frame GMOs as "uncultural." In the French debate, the CP posits culture against a "culturelessness" associated with technoscience and industry-driven foods such as GMOs and McDonald's. [source]

Effect of feeding scheme and prey density on survival and development of Chinese mitten crab Eriocheir sinensis zoea larvae

Li-ying Sui
Abstract The effect of feeding scheme and prey density on survival and development of Eriocheir sinensis zoea larvae was studied in three experiments. Different combinations and densities of rotifers (Brachionus rotundiformis) and newly hatched Artemia nauplii were fed to zoea larvae. Average survival at each stage, larval development (larval stage index, LSI), duration of zoeal stage and individual megalopa dry weight were compared among treatments. This study revealed that, under the experimental conditions, rotifers should be replaced with Artemia between the zoea 3 (Z3) and the zoea 4 (Z4) stage. The optimal rotifer feeding densities for zoea 1 (Z1) and zoea 2 (Z2) were 15 and 20 mL,1 respectively, while the optimal Artemia feeding density for Z3, Z4 and zoea 5 (Z5) was 3, 5 and 8 mL,1 respectively. Further trials in production scale are recommended. [source]

Micro-scale bioreactors that predict production scale

Article first published online: 26 OCT 200
No abstract is available for this article. [source]

Microarray-based gene expression analysis as a process characterization tool to establish comparability of complex biological products: Scale-up of a whole-cell immunotherapy product

Min Wang
Abstract Whole-cell immunotherapies and other cellular therapies have shown promising results in clinical trials. Due to the complex nature of the whole cell product and of the sometimes limited correlation of clinical potency with the proposed mechanism of action, these cellular immunotherapy products are generally not considered well characterized. Therefore, one major challenge in the product development of whole cell therapies is the ability to demonstrate comparability of product after changes in the manufacturing process. Such changes are nearly inevitable with increase in manufacturing experience leading to improved and robust processes that may have higher commercial feasibility. In order to comprehensively assess the impact of the process changes on the final product, and thus establish comparability, a matrix of characterization assays (in addition to lot release assays) assessing the various aspects of the cellular product are required. In this study, we assessed the capability of DNA-microarray-based, gene-expression analysis as a characterization tool using GVAX cancer immunotherapy cells manufactured by Cell Genesys, Inc. The GVAX immunotherapy product consists two prostate cancer cell lines (CG1940 and CG8711) engineered to secrete human GM-CSF. To demonstrate the capability of the assay, we assessed the transcriptional changes in the product when produced in the presence or absence of fetal bovine serum, and under normal and hypoxic conditions, both changes intended to stress the cell lines. We then assessed the impact of an approximately 10-fold process scale-up on the final product at the transcriptional level. These data were used to develop comparisons and statistical analyses suitable for characterizing culture reproducibility and cellular product similarity. Use of gene-expression data for process characterization proved to be a reproducible and sensitive method for detecting differences due to small or large changes in culture conditions as might be encountered in process scale-up or unanticipated bioprocess failures. Gene expression analysis demonstrated that cell products of representative lots under the same production process and at the same production scale were statistically identical. Large process changes that resulted from the artificial stress conditions used (absence of FBS and induction of hypoxia) displayed profoundly different gene expression patterns. We propose the use of simple t -test analysis in combination with the herein introduced expression ratio with mean intensity (ERMI) analysis as useful tools for process characterization by global gene expression analysis. Biotechnol. Bioeng. 2009; 104: 796,808 © 2009 Wiley Periodicals, Inc. [source]

A review of pervaporation for product recovery from biomass fermentation processes,

Leland M Vane
Abstract Although several separation technologies are technically capable of removing volatile products from fermentation broths, distillation remains the dominant technology. This is especially true for the recovery of biofuels such as ethanol. In this paper, the status of an emerging membrane-based technology, called pervaporation, for this application is reviewed. Several issues and research priorities which will impact the ability of pervaporation to be competitive for biofuel recovery from fermentation systems are identified and discussed. They include: increased energy efficiency; reduction of capital cost for pervaporation systems; longer term trials with actual fermentation broths; optimized integration of pervaporation with fermentor; synergy of performing both alcohol recovery and solvent dehydration by pervaporation with dephlegmation fractional condensation technology; and updated economic analyses of pervaporation at various biofuel production scales. Pervaporation is currently viable for biofuel recovery in a number of situations, but more widespread application will be possible when progress has been made on these issues. Published in 2005 for SCI by John Wiley & Sons, Ltd. [source]

The Governance of Networks and Economic Power: The Nature and Impact of Subcontracting Relationships

Silvia Sacchetti
Abstract., Current debate on networking focuses on network structures and firm strategies. In this perspective, theoretical analysis has been concerned with allocative issues. This essay proposes a different interpretation. Starting from the existing theoretical framework, we emphasise the nature and the implications of different types of networks with respect to socio-economic development from a distributional point of view. Within this context, we develop the analysis of subcontracting starting from the concept of economic power. We then provide an analysis of governance in production by considering the attitudes and the nature of the actors involved. The externalisation of activities by large transnationals, which characterises current corporate restructuring, is often related to the search for greater flexibility, but also for greater power over governments, labour, and subcontractors. Differently, networks based on the mutual dependence of actors, which are not necessarily built around a large firm, could , under particular conditions , reach large production scales or more complex scopes without breaking the links with territorial systems, thus including local objectives in the strategic decision-making process. Our conclusion is that the impact of subcontracting networks varies enormously. This is crucial to an understanding of future trends and possibilities. Not least, firms and public policy agencies need to understand the implications of different forms of subcontracting network and how those forms actually differ in practice. [source]

Multivariate data analysis on historical IPV production data for better process understanding and future improvements

Yvonne E. Thomassen
Abstract Historical manufacturing data can potentially harbor a wealth of information for process optimization and enhancement of efficiency and robustness. To extract useful data multivariate data analysis (MVDA) using projection methods is often applied. In this contribution, the results obtained from applying MVDA on data from inactivated polio vaccine (IPV) production runs are described. Data from over 50 batches at two different production scales (700-L and 1,500-L) were available. The explorative analysis performed on single unit operations indicated consistent manufacturing. Known outliers (e.g., rejected batches) were identified using principal component analysis (PCA). The source of operational variation was pinpointed to variation of input such as media. Other relevant process parameters were in control and, using this manufacturing data, could not be correlated to product quality attributes. The gained knowledge of the IPV production process, not only from the MVDA, but also from digitalizing the available historical data, has proven to be useful for troubleshooting, understanding limitations of available data and seeing the opportunity for improvements. Biotechnol. Bioeng. 2010;107: 96,104. © 2010 Wiley Periodicals, Inc. [source]