Purifying biopharmaceuticals: knowledge-based chromatographic process development

Hanke, Alexander T.; Ottens, Marcel

doi:10.1016/j.tibtech.2014.02.001

Cited by 162 publications

(106 citation statements)

References 97 publications

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“…Chromatography is a very mature technology, is widely adopted, and has been reviewed in great detail elsewhere. [8][9][10][11] BioPharma's other workhorse technique for chemical/ compositional analysis is mass spectrometry (MS), a technique that involves the creation of ionized fragments of the target-molecule and the separation of the ions according to their mass-to-charge ratio. [12][13][14] Mass spectrometry techniques are often coupled with chromatographic separation techniques producing methods that have very high analyte resolution which are often the best means of characterizing complex biological samples in detail.…”

Section: Analytical Technologies In the Biopharmaceutical Industrymentioning

confidence: 99%

Applications of Raman Spectroscopy in Biopharmaceutical Manufacturing: A Short Review

2017

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The production of active pharmaceutical ingredients (APIs) is currently undergoing its biggest transformation in a century. The changes are based on the rapid and dramatic introduction of protein-and macromolecule-based drugs (collectively known as biopharmaceuticals) and can be traced back to the huge investment in biomedical science (in particular in genomics and proteomics) that has been ongoing since the 1970s. Biopharmaceuticals (or biologics) are manufactured using biological-expression systems (such as mammalian, bacterial, insect cells, etc.) and have spawned a large (>E35 billion sales annually in Europe) and growing biopharmaceutical industry (BioPharma). The structural and chemical complexity of biologics, combined with the intricacy of cell-based manufacturing, imposes a huge analytical burden to correctly characterize and quantify both processes (upstream) and products (downstream). In small molecule manufacturing, advances in analytical and computational methods have been extensively exploited to generate process analytical technologies (PAT) that are now used for routine process control, leading to more efficient processes and safer medicines. In the analytical domain, biologic manufacturing is considerably behind and there is both a huge scope and need to produce relevant PAT tools with which to better control processes, and better characterize product macromolecules. Raman spectroscopy, a vibrational spectroscopy with a number of useful properties (nondestructive, non-contact, robustness) has significant potential advantages in BioPharma. Key among them are intrinsically high molecular specificity, the ability to measure in water, the requirement for minimal (or no) sample pre-treatment, the flexibility of sampling configurations, and suitability for automation. Here, we review and discuss a representative selection of the more important Raman applications in BioPharma (with particular emphasis on mammalian cell culture). The review shows that the properties of Raman have been successfully exploited to deliver unique and useful analytical solutions, particularly for online process monitoring. However, it also shows that its inherent susceptibility to fluorescence interference and the weakness of the Raman effect mean that it can never be a panacea. In particular, Raman-based methods are intrinsically limited by the chemical complexity and wide analyte-concentration-profiles of cell culture media/bioprocessing broths which limit their use for quantitative analysis. Nevertheless, with appropriate foreknowledge of these limitations and good experimental design, robust analytical methods can be produced. In addition, new technological developments such as time-resolved detectors, advanced lasers, and plasmonics offer potential of new Raman-based methods to resolve existing limitations and/or provide new analytical insights.

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Section: Analytical Technologies In the Biopharmaceutical Industrymentioning

confidence: 99%

Applications of Raman Spectroscopy in Biopharmaceutical Manufacturing: A Short Review

2017

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“…As the fit is performed to the original data, signal distortion, noise amplification and generation of artefacts such as negative side lobes usually associated with Fourier transform chromatogram sharpening are not of major concern here. The comparatively small errors on the peak locations and first moments make the technique well suitable for applications such as component identification or for the regression of thermodynamic parameters [30]. Robust quantitative results are achieved when resolution is sufficient for local maxima to be detected prior to resolution enhancement.…”

Section: Discussionmentioning

confidence: 99%

Fourier transform assisted deconvolution of skewed peaks in complex multi-dimensional chromatograms

Hanke

Verhaert

Wielen

et al. 2015

Journal of Chromatography A

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“…This is associated with a substantial amount of time and reagents needed for the process. One trend in downstream processing of biopharmaceuticals recently is the approach towards development of mechanistic models for better understanding behaviors of proteins on certain chromatography, such as quantitative structure-property relations (QSPR) or molecular dynamics simulations [14]. To obtain necessary protein characteristics, programs are developed for calculation and analysis of molecular properties.…”

Section: Introductionmentioning

confidence: 99%

Purification design and practice for pertactin, the third component of acellular pertussis vaccine, from Bordetella pertussis

Zhang

et al. 2016

Vaccine

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Purifying biopharmaceuticals: knowledge-based chromatographic process development

Cited by 162 publications

References 97 publications

Applications of Raman Spectroscopy in Biopharmaceutical Manufacturing: A Short Review

Applications of Raman Spectroscopy in Biopharmaceutical Manufacturing: A Short Review

Fourier transform assisted deconvolution of skewed peaks in complex multi-dimensional chromatograms

Purification design and practice for pertactin, the third component of acellular pertussis vaccine, from Bordetella pertussis

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