Applications of Raman Spectroscopy in Biopharmaceutical Manufacturing: A Short Review
| Autor: | Kevin Buckley, Alan G. Ryder |
|---|---|
| Přispěvatelé: | Irish Research Council, Science Foundation Ireland |
| Rok vydání: | 2017 |
| Předmět: |
process analytical tool
near-infrared spectroscopy principal component analysis Computer science Process (engineering) Process analytical technology Cell Culture Techniques Nanotechnology CHO Cells 02 engineering and technology aromatic-amino-acids Spectrum Analysis Raman 01 natural sciences induced structural-changes Biopharmaceutics Chemometrics raman spectroscopy Bioreactors Cricetulus Downstream (manufacturing) Cricetinae Animals Humans Process control Bioprocess cell-culture media Instrumentation Spectroscopy Flexibility (engineering) business.industry online monitoring 010401 analytical chemistry mass-spectrometry chemometrics 021001 nanoscience & nanotechnology biopharmaceutical manufacturing Automation proteins process analytical technology Recombinant Proteins Culture Media 0104 chemical sciences cell culture media least-squares methods protein secondary structure Biochemical engineering 0210 nano-technology business |
| Zdroj: | Applied Spectroscopy |
| ISSN: | 1943-3530 0003-7028 |
| DOI: | 10.1177/0003702817703270 |
| Popis: | 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. KB is a Government of Ireland Postdoctoral Fellow and would like to thank the Irish Research Council for their support (Grant no.: GOIPD/2015/88). Some support for KB from the Synthesis and Solid State Pharmaceutical Centre, funded by Science Foundation Ireland and industry partners (Grant no.: 12/RC/2275) is also acknowledged. peer-reviewed |
| Databáze: | OpenAIRE |
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