Near-infrared spectroscopy in compliance with pharma regulations

Significance of the Topic

Near-infrared spectroscopy (NIRS) has become an indispensable secondary analytical technique in pharmaceutical manufacturing. It enables rapid, non-destructive measurement of chemical composition and physical properties, aligning with Process Analytical Technology (PAT) initiatives and pharmacopoeial standards to support quality by design and real-time release testing.

Objectives and Study Overview

This white paper examines how Metrohm NIRS solutions meet stringent regulatory requirements and facilitate analysis throughout the production chain. Key objectives include:

• Demonstrating compliance with FDA, EMA, and USP guidelines.
• Outlining comprehensive workflows for instrument and method validation.
• Presenting practical application examples, from raw material checks to finished dosage form quality.

Methodology and Instrumentation

NIRS exploits diffuse reflectance and transmission spectra to extract multivariate data without sample destruction or extensive preparation. It supports offline, atline, online, and inline modes, covering:

• Identification and conformity testing of incoming materials.
• Real-time monitoring of granulation, drying, and bioreactor processes.
• Assessment of blend homogeneity, moisture content, tablet hardness, and stability.

Used Instrumentation:

• Metrohm NIRS XDS MasterLab spectrometer for transmission and reflection measurements.
• XDS SmartProbe Analyzer enabling atline and inline process integration.
• Vision Air software fully compliant with FDA 21 CFR Part 11 and EU Annex 11 for electronic records.
• Chemometric tool support including Metrohm Vision, CAMO’s Unscrambler, and Eigenvector’s PLS_Toolbox.

Main Results and Discussion

Metrohm NIRS systems undergo full qualification (IQ, OQ, PQ) according to USP<1058> and USP<1119>, with performance criteria for wavelength accuracy, photometric scale, and noise. Software validation ensures secure electronic records and signatures. Method development and validation follow ICH Q2(R1) guidelines, documenting procedures, validation reports, and system suitability criteria. Application studies showcase:

• Rapid identity testing of raw materials directly in warehouses or QC labs.
• Inline measurement of residual solvents and moisture during lyophilization.
• Noninvasive content uniformity and assay of tablets and capsules, even within blister packs.

Benefits and Practical Applications

• Non-destructive and reagent-free analysis preserving sample integrity.
• Minimal or no sample preparation, reducing workflow complexity.
• Simultaneous quantification of multiple parameters for efficient QC.
• Real-time process control, minimizing out-of-specification batches and rework.
• High return on investment through faster release testing and lower operational costs.

Future Trends and Applications

Emerging developments include integration of advanced machine learning for chemometric model robustness, miniaturized and portable NIRS devices for in-field analysis, seamless connection to digital twin platforms, and expanded use in continuous manufacturing and real-time release testing frameworks.

Conclusion

Metrohm’s NIRS platforms deliver a fully validated, regulation-compliant solution for pharmaceutical analysis—from raw material verification through in-process monitoring to final product quality assurance. Combined with expert support and flexible software, these systems empower manufacturers to implement PAT strategies and maintain consistent regulatory adherence.

Reference

• Ciurczak, E. W., & Igne, B. Pharmaceutical and Medical Applications of Near-Infrared Spectroscopy. CRC Press, 2015.
• Broad, N., Graham, P., Hailey, R., Hardy, A., Holland, S., Hughes, S., Lee, D., Prebble, K., Salton, N., & Warren, P. Guidelines for the Development and Validation of Near-Infrared Spectroscopic Methods in the Pharmaceutical Industry. Handbook of Vibrational Spectroscopy, Wiley, 2002.
• Mattes, R., et al. Monitoring viable cell density in bioreactors using near-infrared spectroscopy. BioProcessing Journal, 2010.
• USP <1119>. Near-Infrared Spectroscopy. United States Pharmacopeia 39, 2016.
• Metrohm Application Notes and Bulletins: AN-NIR-002, AN-NIR-014, AN-NIR-016, AN-NIR-017, AB-358, AB-410.