Graphical method for the calculation of chromatographic performance in representing the trade-off between purity and recovery

Ngiam, S.H.; Zhou, Yuhong; Turner, Malcolm E.; Titchener‐Hooker, Nigel J.

doi:10.1016/s0021-9673(01)01299-7

Cited by 16 publications

(20 citation statements)

References 7 publications

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“…In process chromatography, purity and yield are often the two major process outputs to be traded. Ngiam et al (2001) applied fractionation diagrams earlier used by Richardson et al (1990) to address fractional protein precipitation. The basis of the approach is shown in Figure 6.…”

Section: Chromatographymentioning

confidence: 99%

Micro biochemical engineering to accelerate the design of industrial‐scale downstream processes for biopharmaceutical proteins

Titchener‐Hooker

Dunnill

Hoare

2008

Biotech & Bioengineering

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The article examines how a small set of easily implemented micro biochemical engineering procedures combined with regime analysis and bioprocess models can be used to predict industrial scale performance of biopharmaceutical protein downstream processing. This approach has been worked on in many of our studies of individual operations over the last 10 years and allows preliminary evaluation to be conducted much earlier in the development pathway because of lower costs. It then permits the later large scale trials to be more highly focused. This means that the risk of delays during bioprocess development and of product launch are reduced. Here we draw the outcomes of this research together and illustrate its use in a set of typical operations; cell rupture, centrifugation, filtration, precipitation, expanded bed adsorption, chromatography and for common sources, E. coli, two yeasts and mammalian cells (GS-NSO). The general approach to establishing this method for other operations is summarized and new developments outlined. The technique is placed against the background of the scale-down methods that preceded it and complementary ones that are being examined in parallel. The article concludes with a discussion of the advantages and limitations of the micro biochemical engineering approach versus other methods.

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Section: Chromatographymentioning

confidence: 99%

Micro biochemical engineering to accelerate the design of industrial‐scale downstream processes for biopharmaceutical proteins

Titchener‐Hooker

Dunnill

Hoare

2008

Biotech & Bioengineering

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“…The variations of chromatographic performance to changes in operating conditions have previously been evaluated directly from on-line chromatograms. However, these are not that visually informative in quantifying the consequences for performance and sensitivity to changes in operational conditions [9]. The aim of any chromatographic model is to enable accurate prediction of target peak elution times, hence, it should enable determination of the peak cut-points, in order to obtain the required product at the maximum purity and yield.…”

Section: Determination Of Product Purity and Yield Trade-offsmentioning

confidence: 99%

“…The aim of any chromatographic model is to enable accurate prediction of target peak elution times, hence, it should enable determination of the peak cut-points, in order to obtain the required product at the maximum purity and yield. Research within our laboratories has led to the development of a fractionation diagram approach, initially to investigate fractional protein precipitation [11,12], but more recently, as a graphical method for determining chromatographic performance in terms of the process trade-offs between purification and yield [9]. The application of this method to CCC here aims to illustrate the effects of feed type and CCC operating variables on the degree of product enrichment and yield at both the laboratory and pilot scales.…”

Section: Determination Of Product Purity and Yield Trade-offsmentioning

confidence: 99%

“…Our results show that good separation of EA can be achieved with predictable scale-up of operating conditions using a back extract feed. In addition, the application of fractionation diagram theory [9] is presented, which provides a graphical tool for the rapid identification of process trade-offs between the attainable purity and yield achievable by CCC.…”

Section: Introductionmentioning

confidence: 99%

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Antibiotic purification from fermentation broths by counter-current chromatography: analysis of product purity and yield trade-offs

Booth

Ngiam

Lye

2004

Bioprocess Biosyst Eng

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Counter-current chromatography (CCC) is a low pressure, liquid-liquid chromatographic technique which has proven to be a powerful purification tool for the high-resolution fractionation of a variety of active pharmaceutical compounds. The successful integration of CCC into either existing or new manufacturing processes requires the predictable purification of target compounds from crude, fermentation-derived, feed streams. This work examines the feasibility of CCC for the purification of fermentation-derived erythromycin A (EA) from its structurally and chemically similar analogues. At the laboratory scale, the effect of feed pre-treatment using either clarified, forward extracted (butyl acetate) or back extracted broth on EA separation was investigated. This defined the degree of impurity removal required, i.e. back extracted broth, to ensure a reproducible elution profile of EA during CCC. Optimisation and scale-up of the separation studied the effects of mobile phase flow (2-40 ml.min(-1)) and solute loading (0.1-10 g) on the attainable EA purity and yield. The results in all cases demonstrated a high attainable EA purity (>97% w/w) with throughputs up to 0.33 kg.day(-1). Secondly, a predictive scale-up model was applied demonstrating, that from knowledge of the solute distribution ratio of EA (K(EA)) at the laboratory scale, the EA elution time at the pilot scale could be predicted to within 3-10%, depending upon the solute injection volume. In addition, this study has evaluated a "fractionation diagram" approach to visually determine the effects of key operational variables on separation performance. This resulted in accurate fraction cut-point determination for a required degree of product purity and yield. Overall, the results show CCC to be a predictable and scaleable separation technique capable of handling real feed streams.

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“…Baseline separation is not normally achieved in preparative chromatography, therefore, the location of the cut points will determine the purity and yield of the product [11]. In some cases, the components can be detected individually online, but normally only a lumped measurement such as UV absorbance is available.…”

Section: Introductionmentioning

confidence: 99%

Supporting Design and Control of a Reversed‐Phase Chromatography Step by Mechanistic Modeling

Westerberg¹,

Borg²,

Andersson³

et al. 2011

Chem Eng & Technol

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There is a need to design and understand control strategies for biopharmaceutical processes. The control strategy will influence the design space and process performance and should be chosen together with the operating point and design space. Mechanistic modeling is used to design and evaluate control strategies for product pooling in preparative chromatography. A kinetic dispersive model was calibrated to reversed-phase chromatography experiments. Uncorrelated process disturbances were introduced to optimized operating points, and the effects of disturbances were evaluated and reduced by control strategies. Pooling control was implemented at a fixed UV absorbance or as a function of retention volume and UV peak height. The higher flexibility of the second control strategy decreased the loss of yield and productivity caused by the disturbances.

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Graphical method for the calculation of chromatographic performance in representing the trade-off between purity and recovery

Cited by 16 publications

References 7 publications

Micro biochemical engineering to accelerate the design of industrial‐scale downstream processes for biopharmaceutical proteins

Micro biochemical engineering to accelerate the design of industrial‐scale downstream processes for biopharmaceutical proteins

Antibiotic purification from fermentation broths by counter-current chromatography: analysis of product purity and yield trade-offs

Supporting Design and Control of a Reversed‐Phase Chromatography Step by Mechanistic Modeling

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