Differentiating Biopharmaceutical Raw Materials Using Spatially Offset Raman Spectroscopy

Importance of the topic

In biopharmaceutical manufacturing, rapid and reliable verification of incoming raw materials is critical to ensure product quality and supply chain integrity. Past incidents of contamination have underscored the need for non-destructive, through-container inspection methods that meet regulatory expectations and accelerate production workflows.

Objectives and Study Overview

This study evaluated the Agilent Vaya Raman handheld spectrometer, leveraging spatially offset Raman spectroscopy (SORS), to differentiate five classes of biopharma raw materials directly through their storage containers. The goal was to validate its capability to deliver accurate PASS/FAIL identification in under 35 seconds without opening containers.

Methodology and Instrumentation

The experiment involved reagent-grade samples of amino acids, biological buffers, cell culture media, surfactants, and inorganic salts supplied in typical polyethylene, amber, and paper-based containers. No sample preparation was required. Spectra were acquired at room temperature under ambient light with automatic instrument settings. A reference spectrum of the container (“zero offset”) was subtracted from the offset spectrum to isolate the material signal.

Used Instrumentation

The Agilent Vaya Raman handheld spectrometer with a SORS configuration, featuring a CCD detector optimized for low-intensity offset signals.

Main Results and Discussion

• Biological buffers (HEPES, CHES, TRIS): Distinct bands in the 600–1300 cm⁻¹ region enabled clear differentiation based on alicyclic and functional group signatures.
• Surfactants (Triton X-100, PEG, Polysorbate 80): Characteristic peaks at ~1615 cm⁻¹ and ~1650 cm⁻¹ distinguished aromatic and oleate-containing structures.
• Amino acids (alanine, phenylalanine, glycine): Unique markers such as 852 cm⁻¹ for alanine, 1005 cm⁻¹ for phenylalanine, and dual bands at 894 cm⁻¹ and 1327 cm⁻¹ for glycine.
• Cell culture media (RPMI-1640, Ham’s F10): Powdered media profiles reflected high-mass percent Raman-active components, allowing discrimination through clear and translucent vessels.
• Inorganic salts (phosphate derivatives): Protonation and counterion variations yielded distinctive spectra for each salt type.

Benefits and Practical Applications

The SORS-enabled handheld approach delivers rapid, non-destructive ID of raw materials through diverse container types, eliminating sampling booths, preserving sterility, and reducing logistical steps. It supports high-throughput reception processes in biopharma warehouses.

Future Trends and Potential Applications

• Integration with process analytical technology (PAT) frameworks for real-time monitoring.
• Expansion of spectral libraries for broader material coverage.
• Application of machine learning for automated identification and anomaly detection.
• Adoption in downstream quality control and supply chain security stages.

Conclusion

The Agilent Vaya handheld Raman spectrometer employing SORS reliably differentiates biopharmaceutical raw materials through intact containers within seconds, meeting industry demands for speed, accuracy, and compliance. This approach streamlines material handling and enhances quality assurance in biomanufacturing.

References

• Chess EK, Bairstow S, Donovan S, et al. Case study: contamination of heparin with oversulfated chondroitin sulfate. Handbook of Experimental Pharmacology. 2012;207:99-125.
• Spectrochimica Acta Part A. Raman spectra of amino acids and their aqueous solutions. 2011;78:1187-1195.