Faster pharmaceutical process monitoring with FT-NIR spectroscopy

Traditional offline quality testing can delay the detection of process and quality deviations until considerable time and materials have already been invested. Process Analytical Technology (PAT) addresses this challenge through real-time process monitoring, with Fourier transform near-infrared (FT-NIR) spectroscopy playing an increasingly important role. This article examines the technology, its key pharmaceutical applications, and how Hamamatsu Photonics’ latest FT-NIR spectrometer supports the development of reliable PAT solutions.

Pharmaceutical manufacturing requires tight control of every part of the process – including blending powders, granulating intermediates and applying tablet coatings – as even small variations can affect product quality, consistency, and yield. However, in many cases, quality is still confirmed through offline laboratory testing. This often means that, by the time a deviation is detected, considerable manufacturing effort and materials may already have been invested in the batch, potentially resulting in rework, investigations, scrap or delays to product release. Recognizing the need for greater process understanding and more science-based manufacturing, the U.S. Food and Drug Administration (FDA) introduced its PAT initiative.

PAT encourages manufacturers to build quality into manufacturing through better process understanding and real-time monitoring. In practice, it requires the real-time measurement of critical process parameters (CPPs) and critical quality attributes (CQAs) to improve process understanding and control. Achieving this relies on analytical technologies that are fast, robust, and capable of integrating with automated control systems to operate directly alongside the manufacturing process. Among these, near-infrared (NIR) spectroscopy has become one of the most widely adopted techniques, reflected by the FDA's publication of dedicated guidance covering the development, validation, and implementation of NIR analytical procedures for pharmaceutical manufacturing. ^[1-4]

FT-NIR spectroscopy

FT-NIR spectroscopy is commonly used in pharmaceutical PAT. It operates in the short-wave infrared (SWIR) portion of the NIR spectrum (approximately 1,000-2,500 nm), where many organic molecules exhibit characteristic absorption overtones and combination-band absorptions that are highly informative for quantitative chemical analysis.

FT-NIR spectroscopy uses an interferometer to collect information from numerous wavelengths simultaneously, which is then converted into a conventional spectrum by a Fourier transform. In contrast to instruments that measure individual wavelengths sequentially, FT-NIR spectroscopy captures information from the entire spectral range in a single measurement, retaining the rich spectral information required for quantitative analysis. ^[5] The spectra can then be combined with chemometric models to track CQAs.

Depending on the application, measurements can be performed in diffuse reflection or transmission modes, allowing both powders and liquids to be analyzed. This flexibility has made FT-NIR spectroscopy one of the most widely used spectroscopic techniques for pharmaceutical PAT. It is commonly applied to moisture monitoring, blend and content uniformity, and material identification and verification, as well as being used for reaction monitoring, API and excipient concentration measurements, process endpoint determination, tablet coating, crystallization, and solvent analysis. ^[6-8]

Moisture content analysis

Moisture monitoring is one of the most common applications of FT-NIR spectroscopy, as it influences powder flow, granulation behavior, tablet compression, coating performance, and long-term product stability. Frequent spectroscopic measurements provide earlier visibility into changing moisture levels during drying, granulation, and coating than intermittent laboratory sampling.

Absorption spectra of a dry and a wet cloth obtained using a Hamamatsu Photonics FT-NIR spectrometer. The wet cloth has a higher absorption in the 1,450 nm and 1,930 nm water absorption bands.

Figure 1: Absorption spectra of a dry and a wet cloth obtained using a Hamamatsu Photonics FT-NIR spectrometer. The wet cloth has a higher absorption in the 1,450 nm and 1,930 nm water absorption bands.

Blend and content uniformity

Pharmaceutical formulations contain multiple ingredients that must be distributed consistently throughout the product. Each compound produces a characteristic NIR spectral fingerprint, and FT-NIR spectroscopy can be combined with chemometric models to assess blend homogeneity and ingredient distribution throughout the manufacturing process. This provides a more representative assessment than can be achieved using a limited number of discrete samples. ^[9]

Absorption spectra of tablets containing theophylline, caffeine, and additives obtained using a Hamamatsu Photonics FT-NIR spectrometer.

Figure 2: Absorption spectra of tablets containing theophylline, caffeine, and additives obtained using a Hamamatsu Photonics FT-NIR spectrometer.

Material identification and verification

Another important application of FT-NIR spectroscopy is material identification and verification, including for incoming raw material inspection and screening for counterfeit or substituted products. Distinct spectral fingerprints allow ingredients to be identified rapidly before they enter production, helping to reduce the risk of mix-ups. Depending on the packaging material and measurement configuration, inspection may even be possible without opening the package. ^[10]

Spectra of five medicines obtained using a Hamamatsu Photonics FT-NIR spectrometer.

Figure 3: Spectra of five medicines obtained using a Hamamatsu Photonics FT-NIR spectrometer.

Together, these applications show how inline FT-NIR spectroscopy shifts quality assurance from periodic testing to a continuous process. Repeated inline measurements provide a more representative picture of the manufacturing process than isolated laboratory testing, enabling earlier detection of deviations and more automated process control. However, successful implementation relies on continuous maintenance and calibration of the instrument, and use of appropriate chemometric models.

Meeting the needs of pharmaceutical equipment manufacturers

Delivering consistent and reliable FT-NIR spectroscopy measurements in a manufacturing environment is highly dependent on the design of the instrument. Factors such as signal-to-noise ratio, accuracy, throughput, robustness, long-term stability, compactness, cost-effectiveness and ability to integrate with existing hardware and control systems are all crucial to effective inline testing. Compact instrumentation is particularly valuable where space is limited, or where spectroscopy needs to be incorporated into existing production equipment rather than installed as a standalone instrument.

Reducing the engineering effort required to integrate FT-NIR spectrometry into production environments is an important consideration for OEMs developing complete PAT solutions for pharmaceutical manufacturing. Hamamatsu Photonics’ FT-NIR spectrometers are already established in a range of industrial and analytical applications, and the latest generation instrument builds on this proven platform by combining the inherent advantages of Fourier transform spectroscopy with the higher acquisition speeds required for real-time pharmaceutical PAT. Designed as an integration-ready spectroscopy platform, it provides standard communication interfaces that allow OEMs to incorporate it directly into their own analyzer platforms and automated control systems without developing dedicated instrument electronics. Measurement configurations can also be tailored to individual applications using fiber-optic probes and application-specific optical designs, giving equipment manufacturers the flexibility to optimize sampling geometry for different processes.

The spectrometer also draws on Hamamatsu Photonics’ long-standing expertise in indium gallium arsenide (InGaAs) detector technology, delivering the sensitivity and long-term stability required for reliable operation in continuous manufacturing environments. Together, these capabilities provide OEMs with a compact, cost-effective, high-performance spectroscopy platform that can be easily integrated into complete PAT systems, supporting the development of robust, real-time process monitoring solutions.

Hamamatsu Photonics offers a portfolio of NIR/SWIR technologies designed for OEM developers alongside its FT-NIR spectrometer. These include SWIR mini-spectrometers for extremely high-speed measurements with adjustable integration times, and MEMS Fabry-Pérot interferometer (MEMS-FPI) modules with an integrated light source. This broad product range allows OEMs to select the most appropriate analytical technologies for their measurement requirements.

References

^[1] FDA, “Guidance for Industry PAT — A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance”. Accessed Jul. 7, 2026. Available: https://www.fda.gov/media/71012/download

^[2] E. J. Kim et al., “Process Analytical Technology Tools for Monitoring Pharmaceutical Unit Operations: A Control Strategy for Continuous Process Verification”, Pharmaceutics, vol. 13, no. 6, pp. 919, 2021.

^[3] FDA, “Development and Submission of Near Infrared Analytical Procedures”. Accessed Jul. 7, 2026. Available: https://www.fda.gov/regulatory-information/search-fda-guidance-documents/development-and-submission-near-infrared-analytical-procedures

^[4] M. Morton, “A Quality-by-Design (QbD) Approach to Quantitative Near-Infrared Continuous Pharmaceutical Manufacturing”, American Pharmaceutical Review. Accessed Jul. 7, 2026. Available: https://www.americanpharmaceuticalreview.com/featured-articles/36924-a-quality-by-design-qbd-approach-to-quantitative-near-infrared-continuous-pharmaceutical-manufacturing/

^[5] T. Suzuki et al., “Compact FT-NIR spectrometer made through MOEMS technology for industrial applications”, International Conference on Electronics Packaging and Hybrid Bonding Symposium (ICEP-HBS), pp. 11-12, 2026.

^[6] H. Bao and L. Rodriguez-Saona, “Multi-component beer quality control using miniaturized Fourier transform near-infrared systems”, Microchemical Journal, vol. 221, pp. 116996, 2026.

^[7] T. Kisling et al., "Real-Time Monitoring of a Sol–Gel Reaction for Polysilane Production Using Inline NIR Spectroscopy", Langmuir, vol. 39, no. 23, pp. 8153-8162, 2023.

^[8] S. Nakashima et al., "Kinetics of Chlorophyll Degradation in Japanese Maple (Acer palmatum) Leaves with In Situ Heating Visible and Near-Infrared Spectroscopic Monitoring", Life, vol. 15, no. 3, pp. 335, 2025.

^[9] B. Bakri, “Assessment of powder blend uniformity: Comparison of real-time NIR blend monitoring with stratified sampling in combination with HPLC and at-line NIR Chemical Imaging”, European Journal of Pharmaceutics and Biopharmaceutics, vol. 97, pp. 78, 2015.

^[10] Spectroscopy, “NIR Chemical Imaging for Counterfeit Pharmaceutical Products Analysis”, vol. 22, no. 2, 2007.

Faster pharmaceutical process monitoring with FT-NIR spectroscopy

FT-NIR spectroscopy

Moisture content analysis

Blend and content uniformity

Material identification and verification

Meeting the needs of pharmaceutical equipment manufacturers

References

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