Fulfilling Biopharma’s needs using process Raman Spectroscopy

The biopharmaceutical industry is focused on getting life-saving therapies to patients as quickly and safely as possible. Today, innovation in biopharma – led by next-generation technologies and scientific discovery – means that novel therapies, from cell and gene therapies to biologics to vaccines, for often hard-to-treat diseases are coming to market faster than ever before. In fact, the US Food and Drug Administration (FDA) approved the second-highest number of new drugs in 2023, indicating that the industry is entering a post-pandemic era of rapid drug development.

However, this innovation curve doesn’t come without challenges, and the process to bring therapies from the bench to the bedside is full of complexities. The drug development journey requires speed and precision at every stage in the workflow from drug discovery to development to production and quality control. Traditional analytical methods come with challenges, such as labour intensive and lengthy run times, that can cause significant delays in results and could even impact batch-to-batch variability. As biopharma companies look to expedite upstream and downstream workflows, implementing advanced analytical technologies, such as Raman spectroscopy, can create overall efficiencies, ensure precision and quality, and speed time to market.

Implementing advanced analytical technologies, such as Raman spectroscopy, can create overall efficiencies, ensure precision and quality, and speed time to market

Ensuring product quality

Raman spectroscopy is a non-destructive and non-invasive analytical method that is ideal for ultra-fast chemical imaging, and it can be applied in an array of scientific applications. Raman spectrometers help scientists characterise molecular structures by using a laser to produce Raman scattering.  Unique sets of Raman scattering are produced by different types of molecules, and, like a fingerprint, can quickly and reliably be used to identify materials.

Raman spectroscopy offers researchers across industries from biopharma to battery the opportunity to move quickly from sample to answer with minimal prep and ease of use. Innovative process Raman solutions add immense value to the Process Analytical Technology (PAT) workflow as these solutions can enable real-time, accurate spectral results for in-line, at-line, or on-line monitoring, allowing users to collect high-quality data regardless of experience level. For biopharma companies, Raman spectroscopy allows for continuous analysis and real-time data to aid in quick decision-making for reproducible results.

Drug formulation and development

Raman Spectroscopy also plays a vital role in accelerating upstream biopharma workflows by providing in-line monitoring for multiple attributes, such as viable cell density and metabolic response, with critical parameters that offer overall efficiencies.

Researchers can detect deviations in key biomarkers, such as glucose, lactate, and amino acids, in near-real time so that they can take corrective actions to optimise cell growth and protein yield

In the early stages of drug development, biopharma researchers must understand physiological indicators, such as cell viability, nutrient consumption, metabolite production, and growth kinetics. With Raman, researchers can detect deviations in key biomarkers, such as glucose, lactate, and amino acids, in near-real time so that they can take corrective actions to optimise cell growth and protein yield. Quickly obtaining this data allows for precision and quality control throughout the cell culture process, which leads to better outcomes in downstream workflows and in the final drug product.

Downstream outputs, quality control

In downstream workflows, Raman spectroscopy facilitates real-time quantification of proteins and impurities. The data offers continuous measurement in a flow cell arrangement, and when coupled with calibration models based on known concentrations, scientists can accurately determine metabolite levels. This enables timely adjustments to optimise process performance.

Quality control is a critical component of biopharma workflows, as regulators hold drug products to the highest standards of safety

The technique is also effective in monitoring the quality attributes of bioprocess outputs, such as protein products after they are harvested. By analysing Raman spectra, key quality parameters like protein secondary structure, aggregation and glycosylation can be assessed, ensuring the formulation of high-quality biopharmaceuticals. 

Quality control is a critical component of biopharma workflows, as regulators hold drug products to the highest standards of safety. Raman spectroscopy can quickly identify the chemical structure of samples to pinpoint defects and contaminants, helping biopharma companies to maintain product consistency and ensure product integrity.

An era of efficiency

As advances in science and technology allow the biopharma industry to push the boundaries of what’s possible in medicine, there is an urgent need to optimise workflows to ensure that the drugs in the pipeline can get to the patients who need them most. To do this, biopharma requires tools and techniques that allow for faster processing, overall efficiencies, and reliable data.

The non-destructive and non-invasive approach allows for Raman to be used throughout upstream and downstream workflows and in final stages of manufacturing to ensure quality and safety. It can enhance control and optimisation of bioprocessing operations and reduces the reliance on offline sampling and laboratory analysis, saving both time and costs. With more advanced technology integrating into the lab, there's a need for in-line analytical insights, which Raman can provide, to monitor performance and quality.

Ongoing research, collaboration and regulatory support will drive the broader adoption of Raman Spectroscopy. It will continue to evolve as a vital component of biopharmaceutical manufacturing PAT frameworks, contributing to improved process efficiency, product quality and regulatory compliance. Given the technique’s broad and powerful impact, Raman is likely to become a standard in the biopharma toolkit, helping companies get innovative and life-saving medications to patients around the world as fast as possible.

Sudhir Dahal is product manager – Raman Spectroscopy at Thermo Fisher Scientific