The role of Raman spectroscopy in biopharmaceuticals from development to manufacturing

Abstract

Biopharmaceuticals have revolutionized the field of medicine in the types of active ingredient molecules and treatable indications. Adoption of Quality by Design and Process Analytical Technology (PAT) frameworks has helped the biopharmaceutical field to realize consistent product quality, process intensification, and real-time control. As part of the PAT strategy, Raman spectroscopy offers many benefits and is used successfully in bioprocessing from single-cell analysis to cGMP process control. Since first introduced in 2011 for industrial bioprocessing applications, Raman has become a first-choice PAT for monitoring and controlling upstream bioprocesses because it facilitates advanced process control and enables consistent process quality. This paper will discuss new frontiers in extending these successes in upstream from scale-down to commercial manufacturing. New reports concerning the use of Raman spectroscopy in the basic science of single cells and downstream process monitoring illustrate industrial recognition of Raman’s value throughout a biopharmaceutical product’s lifecycle. Finally, we draw upon a nearly 90-year history in biological Raman spectroscopy to provide the basis for laboratory and in-line measurements of protein quality, including higher-order structure and composition modifications, to support formulation development. Graphical abstract

Analysis of Biologics Molecular Descriptors towards Predictive Modelling for Protein Drug Development Using Time-Gated Raman Spectroscopy

“…The secondary structure, also supported by the CD-spectrum (Figure S16), was comprised of α-helices (12) and β-sheets (15). The β-sheets form the core of the protein, while the α-helices form the outside of the protein, especially in its dimeric form [47].…”

“…Label-free methods for evaluating protein folding states, such as infrared spectroscopy, Raman spectroscopy, UV/VIS absorption spectroscopy, fluorescence spectroscopy, and circular dichroism spectroscopy, are relevant to mention as they are utilized as in-line analytical techniques due to their non-invasive nature. A recent review outlines the importance of Raman spectroscopy to biopharmaceuticals in greater detail [15]. However, the sensitivity, robustness, and the ability of these label-free techniques for quantification need to be improved for protein applications.…”

Challenges and Opportunities of Implementing Data Fusion in Process Analytical Technology—A Review

“…Spectroscopic methods (UV-, NIR-, Raman- and Fluorescence spectroscopy) have applications for monitoring several cell culture parameters, such as nutrient and metabolite concentrations, total and viable cell density, product concentration, and product quality [ 61 , 62 ]. Raman spectroscopy is gaining importance in biopharmaceutical manufacturing as a multi-attribute multi-dimensional sensor due to its specificity and compatibility with aqueous solutions [ 63 ]. During the purification of the biomolecules, monitoring of product concentration and impurities is possible with spectroscopic methods [ 64 ].…”

Raman Spectroscopy Analysis of Coronary Dentin of Vital and Endodontically Treated Teeth

“…It provides information about the chemical content of the studied samples, such as biological/biomedical specimens in cancer research, medications in the pharmaceutical industry and, more recently, neuroscience. [1][2][3] The method utilizes energy from infrared electromagnetic waves in the scope between 300 MHz -3 GHz. Part of the electromagnetic radiation is absorbed by the molecules of the studied sample.…”