Verifying Raw Materials Using Spatially Offset Raman Spectroscopy

Importance of the Topic

Ensuring the correct identity of raw materials is critical in pharmaceutical and biopharmaceutical manufacturing to prevent costly errors and maintain product quality. Noninvasive spectroscopic verification through containers preserves sterility, reduces waste, and accelerates QC workflows.

Objectives and Overview of Study

This technical overview presents spatially offset Raman spectroscopy (SORS) as a solution for raw material identity verification (RMID) through opaque or fluorescent packaging. It explains the SORS principle, demonstrates its performance on common containers, and outlines Agilent’s instrument platforms.

Methodology and Instrumentation

SORS acquires two Raman spectra at different spatial offsets on a container surface:

• Zero offset: Laser and detector co-aligned to capture a container-rich spectrum.
• Offset measurement: Detector is shifted millimeters away to collect a subsurface spectrum enriched in the material signal.
• Scaled subtraction removes container contributions, isolating the pure content spectrum for matching against a reference library.

Used Instrumentation:

• Agilent Vaya handheld Raman system with SORS technology for rapid screening of vials, tubs, sacks, and bottles.
• Agilent RapID portable wheeled Raman system optimized for thick, highly opaque containers.

Main Results and Discussion

SORS successfully retrieved high-quality Raman spectra of sucrose through a 1.5 mm thick polypropylene tub in seconds, outperforming conventional Raman, which failed under the same conditions. The container signal was effectively suppressed, allowing unambiguous identification of the internal contents. SORS handles various materials including plastics, paper sacks, colored glass, and liners, regardless of fluorescence or opacity.

Benefits and Practical Applications

Key advantages of SORS for RMID include:

• Noninvasive testing through sealed packaging without sampling or opening.
• Maintenance of sterility and original storage conditions.
• Elimination of powder booths, protective gear, and cleanup.
• Ability to perform 100 % inspection and multi-point sampling on single containers.
• Compatibility with GMP workflows and 21 CFR Part 11 compliance.

Future Trends and Utilization Opportunities

Emerging directions for container-penetrating Raman spectroscopy include integration into automated warehouse systems, real-time data analytics with machine learning for improved identification accuracy, and expansion to inline QC during manufacturing. Miniaturization and cost reduction of SORS instruments will broaden adoption across industrial sectors.

Conclusion

Spatially offset Raman spectroscopy offers a robust, rapid, and noninvasive approach to verify raw materials within sealed packaging. By eliminating container interferences and preserving material integrity, SORS streamlines QC operations, enhances throughput, and reduces waste in pharmaceutical and biopharmaceutical environments.

Reference

1. Agilent Technologies, Inc. Technical Overview: Verifying Raw Materials Using Spatially Offset Raman Spectroscopy, 2020.