Differentiating Biopharmaceutical Raw Materials Using Spatially Offset Raman Spectroscopy

Significance of the Topic

Ensuring the integrity and rapid verification of biopharmaceutical raw materials is critical to maintain continuous production and to prevent supply disruptions or contamination events such as the heparin scandal of 2008. Spatially offset Raman spectroscopy applied through container walls offers a noninvasive, rapid screening approach suitable for high-volume warehouse operations.

Aims and Study Overview

This study demonstrates the capability of a handheld Agilent Vaya Raman instrument employing SORS to differentiate five classes of raw materials directly through their original containers. The classes include biological buffers, surfactants, amino acids, cell culture media, and inorganic salts. The objective is to reduce sampling time and logistical complexity while delivering reliable identity confirmation at the point of receipt.

Methodology and Instrumentation

Spatially offset Raman spectroscopy uses an offset between illumination and collection points to preferentially collect subsurface Raman signals and subtract container contributions. The Agilent Vaya handheld spectrometer integrates this approach with a sensitive CCD detector and automated acquisition routines. Samples were measured without opening their manufacturer containers under ambient light and at room temperature. Each scan required less than 35 seconds and a performance qualification was conducted prior to measurements.

Main Results and Discussion

Distinct Raman signatures were obtained for each material class through various container types. Biological buffers HEPES, CHES, and TRIS exhibited unique aliphatic and ring vibration bands in the 600–1300 cm-1 region. Surfactants Triton X100, polyethylene glycol, and polysorbate 80 were differentiated by characteristic aromatic and monooleate bands near 1615 and 1650 cm-1. Amino acids alanine, glycine, and phenylalanine showed resolvable markers such as C–C and ring breathing modes. Dry cell culture media RPMI-1640 and Ham’s F10 powders were distinguished by their high-intensity Raman-active components. Inorganic phosphate salts were successfully identified despite variation in protonation and counterions.

Benefits and Practical Applications

• Elimination of container opening and sampling booths
• Reduction of sterility risk and spoilage
• Rapid PASS/FAIL answers at reception
• Streamlined warehouse workflows and improved throughput

Future Trends and Opportunities

Further development may include expansion of spectral libraries to cover broader raw material portfolios, integration with laboratory information systems and PAT frameworks, application of chemometric and machine learning models for automated classification, and miniaturization for broader on-line process monitoring.

Conclusion

The handheld Vaya Raman system using spatially offset Raman spectroscopy enables rapid, accurate identification of biopharmaceutical raw materials through original containers, supporting efficient quality control and supply chain security in upstream processes.

References

1. Chess EK et al Case study contamination of heparin with oversulfated chondroitin sulfate Handbook of Experimental Pharmacology 2012 207 99-125
2. Raman Spectra of Amino Acids and their aqueous solutions Spectrochimica Acta Part A 78 2011 1187-1195