Fujifilm and HORIBA Co-Develop High-Sensitivity Inline Raman Measurement System for Real-Time Visualization of Cultivation and Purification Processes in Biopharmaceutical Manufacturing

Fujifilm Holdings Corporation (Headquarters: Minato-ku, Tokyo; President and CEO: Teiichi Goto) and HORIBA, Ltd. (Headquarters: Minami-ku, Kyoto; President: Masayuki Adachi) have jointly developed a 'High-Sensitivity Inline Raman Measurement System' that continuously and in real time visualizes the concentration of components inside tanks and equipment during the cultivation and purification processes of biopharmaceutical manufacturing. When managing the purification process of antibody drug production using this measurement system, an approximately 10% improvement in antibody yield was confirmed compared to conventional management using UV-Vis spectrophotometry.

Fujifilm will exhibit this measurement system at the 'BIO International Convention' to be held in San Diego, USA, from June 22 to 25, 2026.

Biopharmaceuticals are medicines based on biomolecules such as proteins, advancing into diverse and sophisticated modalities including antibody drugs and cell and gene therapies. These medicines are used to treat a wide range of diseases such as cancer and immune disorders, with the market growing at an annual rate of approximately 9%. In the manufacturing process of biopharmaceuticals, even slight fluctuations in conditions—such as oxygen concentration in culture or purification solutions—can significantly affect product quality and yield. Therefore, various components are identified and analyzed during cultivation and purification processes. However, current offline analysis methods, which involve sampling culture or purification solutions during manufacturing, make it difficult to analyze changes in component concentrations in real time. Against this backdrop, there is increasing demand for high-sensitivity measurement technologies capable of analyzing the state inside tanks and equipment in real time and capturing changes with high precision.

The system developed by the two companies combines a high-sensitivity Raman spectrometer, a high-light-collection-efficiency single-use probe, and a proprietary measurement algorithm. By integrating Fujifilm’s optical design technologies from its photography and optical devices business, along with its expertise in biopharmaceutical manufacturing from its bio CDMO operations, with HORIBA’s highly sensitive, accurate, and stable Raman spectroscopy technology, the companies have developed the 'High-Sensitivity Inline Raman Measurement System,' achieving industry-leading sensitivity. This enables high-precision, real-time visualization of changes in the composition of culture and purification solutions.

Going forward, both companies will proceed with implementation verification of the measurement system toward early practical application. Furthermore, they aim to contribute to the stable production of high-quality biopharmaceuticals—including antibody drugs—and to reducing manufacturing costs through process visualization and the establishment of advanced data analysis technologies.

※1 Raman spectroscopy (a technique that reveals the structure and composition of substances by analyzing scattered light) applied to manufacturing processes, enabling non-destructive, continuous, real-time inline measurement of chemical composition and reaction states without extracting samples.

※2 A method of analyzing component concentration and characteristics by irradiating a sample with ultraviolet or visible light and measuring the amount of light absorbed (absorbance).

※3 Verified through Fujifilm’s model experimental system.

※4 Fujifilm estimate based on Evaluate Pharma (January 15, 2026).

※5 An optical probe that efficiently collects light to enhance measurement sensitivity, and features a simple, single-use design that reduces contamination risk and eliminates the need for cleaning.

※6 As of June 2026, based on Fujifilm’s evaluation. Measured by SN ratio in commercially available inline Raman measurement systems combining Raman spectrometers and probes.

SN Ratio: An indicator showing the ratio of measurement signal (Signal) to noise (Noise). A higher value enables accurate detection of weak signals, making it a critical performance metric for high-sensitivity component analysis.

1. Key Features of the 'High-Sensitivity Inline Raman Measurement System'

The system combines HORIBA’s Raman spectrometer with Fujifilm’s proprietary single-use probe and measurement algorithm. This enables highly efficient acquisition of weak Raman signals and high-precision analysis.

The Raman spectrometer from HORIBA used in this system has a proven track record in the refining processes of the oil industry, where stable monitoring under harsh conditions is required, and features robustness suitable for long-term operation. Additionally, its proprietary noise-reduction design minimizes signal fluctuations caused by temperature increases, and its automatic calibration function corrects measurement drift due to temperature changes, enabling high-precision continuous measurement.

By combining this with Fujifilm’s proprietary optical design technology to create a high-light-collection-efficiency probe with materials and shape optimized for biopharmaceutical manufacturing, the system achieves industry-leading sensitivity by enabling the detection of weak signals previously difficult to capture. The ability to ensure sufficient accuracy even with short measurement times contributes to improved measurement throughput (faster processing).

Furthermore, Fujifilm’s proprietary measurement algorithm enables high-precision, continuous measurement of time-dependent changes in culture solution components and the concentrations of target substances and impurities in purification solutions. It does so by extracting characteristic wavenumbers originating from the measurement target from the acquired Raman spectra and constructing a measurement model.

[Overview of the High-Sensitivity Inline Raman Measurement System] A high-light-collection-efficiency probe and a noise-reduction-designed Raman spectrometer acquire high-SN-ratio Raman spectra. Characteristic wavenumbers derived from the target substance are extracted from the spectra, and a measurement model is constructed to visualize the concentrations of target substances and impurities in real time.

2. Application Examples of the 'High-Sensitivity Inline Raman Measurement System'

• Improved Antibody Yield in Purification Processes of Antibody Drug Manufacturing

Conventional UV-Vis spectrophotometry-based process management allows analysis of total protein content but struggles to distinguish between antibodies (proteins) and impurities with similar compositions. This system leverages high-SN-ratio Raman spectra obtained by combining the Raman spectrometer and single-use probe to extract, via measurement algorithms, the respective wavenumbers originating from antibodies and impurities. Based on this, a measurement model is constructed, enabling differentiation and high-precision, continuous measurement of antibody and impurity concentrations. This allows antibody recovery at the optimal timing when antibody concentration peaks, while keeping impurity concentrations within acceptable limits. Experiments using this system confirmed an approximately 10% improvement in yield compared to conventional UV-Vis spectrophotometry-based process management. For other biopharmaceuticals beyond antibody drugs, the system is also expected to contribute to improved quality and yield by enabling high-sensitivity discrimination between target products and impurities.

3. Application Value and Future Development of the 'High-Sensitivity Inline Raman Measurement System'

• Quality Stabilization in the Cultivation Process of Biopharmaceutical Manufacturing

In cultivation processes, multiple amino acids in the culture solution can be identified and continuously measured, enabling analysis and visualization of time-dependent changes in tank composition. This allows identification of variation factors across different batches or within the same batch process, contributing to stable production of high-quality biopharmaceuticals through precise control of production processes.

• Acceleration of Process Development in Biopharmaceutical Manufacturing

Continuous, real-time inline analysis enables