Raman spectroscopy has advanced from a specialized research tool to a practical, real-time process technology. As Janam Pandya, Process Raman portfolio Product Manager at Thermo Fisher Scientific, observes, “Raman spectroscopy is gaining a lot of traction for process analytical technology (PAT) in the pharmaceutical and biopharmaceutical sectors.” Its growing role reflects the emphasis on manufacturers to improve control, reduce failures, and accelerate decision-making.
Real-Time Insight for High-Risk Bioprocessing
Bioreactors sit at the heart of biopharmaceutical production, housing cells that produce therapeutic biologics. In these vessels, small shifts in nutrients, metabolites, or cell health can push a run off course. Manufacturers need clarity about these factors to prevent costly failures.
Raman delivers that view directly from inside the vessel. “A Raman probe inserted into the bioreactor tracks cell growth, nutrient consumption, and metabolite production as they occur”, explains Pandya. “The main driver is to understand process dynamics in real time so you can save the batch, improve yield, and protect product quality.”
One of the most critical challenges in bioprocessing is avoiding batch contamination. Even minor breaches in sterility can compromise an entire production run—leading to significant financial loss, wasted materials, and potential supply disruptions. Immersion probes designed for sterilization, such as autoclave, safeguard against this risk, maintaining aseptic conditions throughout the process. Alternatively, single-use Raman probes eliminate cross-contamination concerns entirely, ensuring each batch begins with a clean, validated measurement interface. Both approaches give manufacturers the confidence that real-time insights won’t come at the expense of sterility or product integrity.
Removing Bottlenecks in Pharmaceutical Workflows
Pharmaceutical labs face parallel challenges. Traditional dissolution testing for active pharmaceutical ingredients (APIs) depends on frequent sampling and offline analysis with high-performance liquid chromatography (HPLC) or gas chromatography (GC). “Offline testing doesn’t give you constant insight. It’s manual, it compromises sterility, it requires staff around the clock, and the consumables are expensive,” notes Pandya.
He adds that Raman counters these bottlenecks by supplying continuous, in-process measurements. Fewer samples, lower operating costs, and steadier processes follow when teams no longer rely solely on constant offline checks.
Why Raman Excels Where Other Techniques Struggle
Several features position Raman as a strong choice when compared with other technologies, for both bioprocessing and drug development.
“Water becomes noise for near-infrared spectroscopy (NIR), but Raman doesn’t produce strong signals from water,” highlights Pandya. This makes Raman spectroscopy a valuable tool for analyzing aqueous media.
“Raman spectroscopy is also very specific,” he adds. It provides such detailed information that Fourier transform infrared spectroscopy (FTIR) or nuclear magnetic resonance spectroscopy (NMR) sometimes can’t.” This includes amino acid composition, protein structure, and crystalline vs. amorphous API forms—data that informs stability and performance decisions.
Regulatory Barriers—and Signs of Progress
Although Raman offers tangible value, adoption in current good manufacturing practice (cGMP) environments has been delayed. “Pharma is slow to adapt to change. Any new technology needs thorough validation, inspection, and FDA acceptance,” reports Pandya.
Despite this, progress is happening. “I’ve seen communication from FDA specific to glucose monitoring using Raman in upstream bioprocess applications,” he shares. Interest from major pharmaceutical companies suggests that more applications will gain acceptance.
Smarter Instruments and Automated Data Workflows
Technical barriers that once slowed Raman adoption are fading. Legacy Raman tools were large, slow to start, and difficult to calibrate. Modern instruments solve these issues. “Some analyzers are now as small as a laptop instead of needing five feet of bench space,” remarks Pandya.
He adds that Raman spectroscopy instruments, such as the MarqMetrix All-In-One Process Raman Analyzer, are becoming increasingly easy to use. “They’re becoming plug-and-play. Bring the instrument in, press a button, and start running.”
Interpretation of measurements is also becoming easier. While chemometric model development is necessary for interpreting Raman spectra, it has traditionally slowed new projects. “Chemometrics can be overwhelming for someone starting out.” However, Pandya points out that machine learning now accelerates method creation and reduces the expertise required to get started.
Driving Pharma 4.0 Through Closed-Loop Control
Raman spectroscopy now supports automated control systems that adjust processes on the fly.
Pandya describes bioreactor feeding as an example. “Raman can monitor glucose concentration and feed that data into a process control system. In a closed-loop setup, glucose levels trigger automated pump actuation to maintain optimal nutrient levels and prevent cell starvation,” he explains.
Compatibility with major control platforms, such as Emerson, Rockwell, and Siemens, further strengthens this integration. Support for key communication standards also helps. These include open platform communications unified architecture (OPC UA), Modbus, and representational state transfer application programming interface (REST API).
The Road Ahead
Raman spectroscopy continues to shrink, simplify, and integrate into automated environments. AI accelerates method development, while improved connectivity supports real-time release and autonomous control strategies.
Pandya sees a clear trajectory. “Real-time monitoring, real-time release, and tighter process control—that’s where Raman is headed.”