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- Degerman, Marcus, et al.
(författare)
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A Model-Based Approach to Determine the Design Space of Preparative Chromatography
- 2009
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Ingår i: Chemical Engineering & Technology. - : Wiley. - 1521-4125 .- 0930-7516. ; 32:8, s. 1195-1202
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Tidskriftsartikel (refereegranskat)abstract
- A dream of many pharmaceutical companies is to be able to register a large design space with the regulatory agencies. The problem is that this will require both time and money, so an intelligent method of validating a design space is needed. The design space should only cover operating points at which the process runs optimally. This means that the process should be optimized for different process scenarios and objective functions and the found operating points should be registered as design space. This paper presents a method of determining a good design space by creating Pareto fronts for the ideal case and for various process disturbance scenarios. Optimal operating points are found for varying ratios between feed costs and operating costs, making it possible to make a quantitative choice of an operating point based on this ratio and a qualitative choice based on the whole front. The analysis will show how the chromatographic process can be made more robust when optimizing for higher yields, and how the effect of the critical process parameters can change. To be certain that a robust process is found and that it has a high performance, process disturbances must be taken into account when optimizing a process.
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| 2. |
- Degerman, Marcus, et al.
(författare)
-
Determining Critical Process Parameters and Process Robustness in Preparative Chromatography - A Model-Based Approach
- 2009
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Ingår i: Chemical Engineering & Technology. - : Wiley. - 1521-4125 .- 0930-7516. ; 32:6, s. 903-911
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a model-based method to aid in the process validation for the purification of pharmaceutical drugs. The critical process parameters are identified by simulating process disturbances, and this information is then used to determine if the process control space is robust. Simulations are chosen to analyze the entire control space to also find nonlinearities and interaction effects between the process disturbances, which are used to determine where in the control space the critical quality attributes are the lowest, i.e., the worst case scenario. The real process conditions are estimated by running simulations according to plausible probability distributions using Latin hypercube sampling. The probability of batch failure can be estimated from this and it is shown that the worst case scenario is improbable for most cases. This information can help in planning validation experiments or determine which critical process parameters need a tighter control. Three case studies are used to illustrate the usefulness of the methods. It was found that the main critical process parameters in all three case Studies were variations in the modifier concentrations, for example, salt in ion-exchange chromatography and hydrophobic interaction chromatography, and the organic modifier in reversed-phase chromatography.
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| 3. |
- Ohman, Marcus C., et al.
(författare)
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Offshore windmills and the effects electromagnetic fields an fish
- 2007
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Ingår i: Ambio. - 0044-7447 .- 1654-7209. ; 36:8, s. 630-633
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Tidskriftsartikel (refereegranskat)abstract
- With the large scale developments of offshore windpower the number of underwater electric cables is increasing with various technologies applied. A wind farm is associated with different types of cables used for intraturbine, array-to-transformer, and transformer-to-shore transmissions. As the electric currents in submarine cables induce electromagnetic fields there is a concern of how they may influence fishes. Studies have shown that there are fish species that are magneto-sensitive using geomagnetic field information for the purpose of orientation. Thin implies that if the geomagnetic field is locally altered it could influence spatial patterns in fish. There are also physiological aspects to consider, especially for species that are less inclined to move as the exposure could be persistent in a particular area. Even though studies have shown that magnetic fields could affect fish, there is at present limited evidence that fish are influenced by the electromagnetic fields that underwater cables from wind-mills generate. Studies on European eel in the Baltic Sea have indicated some minor effects. In this article we give an overview on the type of submarine cables that are used for electric transmissions in the sea. We also describe the character of the magnetic fields they induce. The effects of magnetic fields on fish are reviewed and how this may relate to the cables used for offshore wind power is discussed.
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| 4. |
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