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Process Streams (process + stream)
Selected AbstractsRapid whole monoclonal antibody analysis by mass spectrometry: An Ultra scale-down study of the effect of harvesting by centrifugation on the post-translational modification profile,BIOTECHNOLOGY & BIOENGINEERING, Issue 1 2010C.Q. Reid Abstract With the trend towards the generation and production of increasing numbers of complex biopharmaceutical (protein based) products, there is an increased need and requirement to characterize both the product and production process in terms of robustness and reproducibility. This is of particular importance for products from mammalian cell culture which have large molecular structures and more often than not complex post-translational modifications (PTMs) that can impact the efficacy, stability and ultimately the safety of the final product. It is therefore vital to understand how the operating conditions of a bioprocess affect the distribution and make up of these PTMs to ensure a consistent quality and activity in the final product. Here we have characterized a typical bioprocess and determined (a) how the time of harvest from a mammalian cell culture and, (b) through the use of an ultra scale-down mimic how the nature of the primary recovery stages, affect the distribution and make up of the PTMs observed on a recombinant IgG4 monoclonal antibody. In particular we describe the use of rapid whole antibody analysis by mass spectrometry to analyze simultaneously the changes that occur to the cleavage of heavy chain C-terminal lysine residues and the glycosylation pattern, as well as the presence of HL dimers. The time of harvest was found to have a large impact upon the range of glycosylation patterns observed, but not upon C-terminal lysine cleavage. The culture age had a profound impact on the ratio of different glycan moieties found on antibody molecules. The proportion of short glycans increased (e.g., (G0F)2 20,35%), with an associated decrease in the proportion of long glycans with culture age (e.g., (G2F)2 7,4%, and G1F/G2F from 15.2% to 7.8%). Ultra scale-down mimics showed that subsequent processing of these cultures did not change the post-translational modifications investigated, but did increase the proportion of half antibodies present in the process stream. The combination of ultra scale-down methodology and whole antibody analysis by mass spectrometry has demonstrated that the effects of processing on the detailed molecular structure of a monoclonal antibody can be rapidly determined early in the development process. In this study we have demonstrated this analysis to be applicable to critical process design decisions (e.g., time of harvest) in terms of achieving a desired molecular structure, but this approach could also be applied as a selection criterion as to the suitability of a platform process for the preparation of a new drug candidate. Also the methodology provides means for bioprocess engineers to predict at the discovery phase how a bioprocess will impact upon the quality of the final product. Biotechnol. Bioeng. 2010;107: 85,95. © 2010 Wiley Periodicals, Inc. [source] Exploiting the intracellular compartmentalization characteristics of the S. cerevisiae host cell for enhancing primary purification of lipid-envelope virus-like particlesBIOTECHNOLOGY PROGRESS, Issue 1 2010Gaik Sui Kee Abstract This article demonstrates how the intracellular compartmentalization of the S. cerevisiae host cell can be exploited to impart selectivity during the primary purification of lipid-envelope virus-like particles (VLPs). The hepatitis B surface antigen (HBsAg) was used as the VLP model in this study. Expressed HBsAg remain localized on the endoplasmic reticulum and the recovery process involves treating cell homogenate with a detergent for HBsAg liberation. In our proposed strategy, a centrifugation step is introduced immediately following cell disruption but prior to the addition of detergent to allow the elimination of bulk cytosolic contaminants in the supernatant, achieving ,70% reduction of contaminating yeast proteins, lipids, and nucleic acids. Recovery and subsequent treatment of the solids fraction with detergent then releases the HBsAg into a significantly enriched product stream with a yield of ,80%. The selectivity of this approach is further enhanced by operating under moderate homogenization pressure conditions (,400 bar). Observed improvements in the recovery of active HBsAg and reduction of contaminating host lipids were attributed to the low-shear conditions experienced by the HBsAg product and reduced cell fragmentation, which led to lower coextraction of lipids during the detergent step. As a result of the cleaner process stream, the level of product capture during the loading stage of a downstream hydrophobic interaction chromatography stage increased by two-fold leading to a concomitant increase in the chromatography step yield. The lower level of exposure to contaminants is also expected to improve column integrity and lifespan. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2010 [source] A Critical Review of Milk Fouling in Heat ExchangersCOMPREHENSIVE REVIEWS IN FOOD SCIENCE AND FOOD SAFETY, Issue 2 2006Bipan Bansal ABSTRACT Fouling of heat exchangers is a problem in the dairy industry and costs billions of dollars every year. It has been studied extensively by researchers around the world, and a large number of studies are reported in the literature. This review focuses on the mechanisms of milk fouling, investigating the role of protein denaturation and aggregation as well as mass transfer. We also endeavor to review the effect of a number of factors which have been classified into 5 categories: (1) milk quality, (2) operating conditions, (3) type and characteristics of heat exchangers, (4) presence of microorganisms, and (5) transfer of location where fouling takes place. Different aspects have been discussed with the view of possible industrial applications and future direction for research. It may not be possible to alter the properties of milk since they are dependent on the source, collection schedule, season, and many other factors. Lowering the surface temperature and increasing the flow velocity tend to reduce fouling. Reducing the heat transfer surface roughness and wettability is likely to lower the tendency of the proteins to adsorb onto the surface. The use of newer technologies like microwave heating and ohmic heating is gaining momentum because these result in lower fouling; however, further research is required to realize their full potential. The presence of microorganisms creates problem. The situation gets worse when the microorganisms get released into the process stream. The location where fouling takes place is of paramount importance because controlling fouling within the heat exchanger may yield little benefit in case fouling starts taking place elsewhere in the plant. [source] Use of paired fathead minnow (Pimephales promelas) reproductive test.ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2006Part 2: Source identification of biological effects at a bleached kraft pulp mill Abstract Reproductive effects of pulp mill effluents on fish continue to be reported in Canadian waters. Spawning delays, reduced gonad size, and altered levels of sex steroid hormones have been found in both sexes of various fish species exposed to effluents. We initiated a project to identify the source/cause of such effects. In part 1 of this two-part series, we exposed mature adult fathead minnow (FHM; Pimephales promelas) for 21 d to final treated effluent (1% and 100% v/v) from a bleached kraft pulp mill in Terrace Bay (ON, Canada). Results suggested pulp mill effluent from this mill affected reproductive indicators in FHM and effects were dependent on effluent concentration, duration of exposure, and method of data analysis. The main objective of this paper was to use the FHM assay to identify waste stream sources within the mill that affect reproductive indicators. Various process streams were selected, characterized with respect to effluent chemistry and acute toxicity, and a subset was tested on-site with the 21-d FHM bioassay. Results showed that both the combined mill effluent (before secondary treatment) and the combined alkaline stream (CALK) caused both decreased spawning events (,55% for both streams) and decreased egg production (28 and 74%, respectively), and the CALK stream resulted in significant male ovipositor development. By comparing response patterns we were able to identify the CALK stream as a source of compounds at this mill affecting reproductive indicators in FHM and highlight this stream for further toxicity identification evaluation. [source] A property-based optimization of direct recycle networks and wastewater treatment processesAICHE JOURNAL, Issue 9 2009José María Ponce-Ortega Abstract This article presents a mathematical programming approach to optimize direct recycle-reuse networks together with wastewater treatment processes in order to satisfy a given set of environmental regulations. A disjunctive programming formulation is developed to optimize the recycle/reuse of process streams to units and the performance of wastewater treatment units. In addition to composition-based constraints, the formulation also incorporates in-plant property constraints as well as properties impacting the environment toxicity, ThOD, pH, color, and odor. The MINLP model is used to minimize the total annual cost of the system, which includes the cost for the fresh sources, the piping cost for the process integration and the waste stream treatment cost. An example problem is used to show the application of the proposed model. The results show that the simultaneous optimization of a recycle network and waste treatment process yields significant savings with respect to a commonly-used sequential optimization strategy. © 2009 American Institute of Chemical Engineers AIChE J, 2009 [source] Reactive chemicals emergency response and post-event calorimetric testingPROCESS SAFETY PROGRESS, Issue 1 2010David Frurip Abstract A serious upset in process conditions may result in a Reactive Chemicals incident. In such an emergency, procedures must be implemented to prevent injuries, mitigate the event and minimize property loss and/or environmental release as dictated by the required facility Emergency Plan. This article describes the process the Dow Chemical Company uses for engaging Reactive Chemicals experts in an emergency situation. In order to be effective, the Reactive Chemicals expert must have or be provided with in-depth knowledge of the process streams and raw materials involved. The information is crucial for understanding what is happening, what might happen in the immediate future, and what can be done to successfully mitigate the Reactive Chemicals incident. Following the incident, calorimetric experiments are typically performed to confirm or refute the hypotheses of what caused the event; additionally, the experiments provide information as to reactive chemicals hazards that may potentially still exist in the process streams. The aforementioned process will be illustrated by describing an actual event. Useful methods are described and recommended for (a) characterizing and storing reactive chemicals, and (b) responding and mitigating safety incidents with reactive chemicals. The role of a reactive chemicals "expert" during and after a plant emergency is important and potentially critical to the safe handling of an ongoing event and also in determining the root cause of the incident. © 2009 American Institute of Chemical Engineers Process Saf Prog, 2010 [source] Exergoeconomic Analysis of Heat Exchanger Networks for Optimum Minimum Approach TemperatureCHEMICAL ENGINEERING & TECHNOLOGY (CET), Issue 2 2008J. Zun-long Abstract Heat exchanger networks (HENs) design for optimum minimum approach temperature is presented using exergoeconomic analysis. Cold and hot utilities are integrated with process streams into T-H plots, forming balanced composite curves, based on pinch technology. Exergy consumption of heat transfer in HENs is calculated using subsection integral on balanced composite curves. Exergy consumption expense substitutes utilities cost as operating cost. The objective function based on exergoeconomics is proposed, which determines the optimum minimum approach temperature of HENs. Numerical results in the cases demonstrate the validity of the proposed approach. Some measures of decreasing energy consumption are disclosed in the dealing process as well. [source] Incorporation of Flexibility in the Design of a Methanol Synthesis Loop in the Presence of Catalyst DeactivationCHEMICAL ENGINEERING & TECHNOLOGY (CET), Issue 6 2003M.R. Rahimpour Abstract This paper presents the incorporation of process flexibility into a methanol synthesis loop operating under catalyst deactivation. A design methodology is discussed with regard to catalyst deactivation, and some limitations are identified. In the current flexibility study the size of the reactor and recycle ratio have been fixed. Attempts to maintain methanol production at the rates observed with fresh catalyst included increased pressure, increased make up gas flow rate, and the injection of carbon dioxide into the make up gas at optimized inlet temperature. In order to provide flexibility and produce a design compatible with increased production rates, the effect of interrelating equipment had to be considered. As a result of catalyst deactivation, an increased flow rate is necessary and the altered process streams entering the preheater disturb the reactor inlet temperature. These issues should be considered in the design stage and may be resolved by the flexible designs presented. [source] | |||||||||||||