著者

Keita Yaginuma Shuichi Tanabe Manabu Kano

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.70, no.1, pp.74-81, 2022-01-01 (Released:2022-01-01)

参考文献数

23

被引用文献数

1

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Soft sensors are powerful tools for the implementation of process analytical technology (PAT). They are categorized into white-box (first-principle), black-box (statistical), and gray-box models. Gray-box models integrate white-box and black-box models to address each drawback, i.e., prediction accuracy and intuitiveness. Although they have been applied to various industrial processes, their applicability to water content monitoring in fluidized bed granulation has not been reported. In this study, we evaluated three types of gray-box models, i.e., parallel, serial, and combined gray-box models, in terms of prediction accuracy using real operating data on a commercial scale with two formulations. The gray-box models were constructed by integrating the heat and mass balance model (white-box model) and locally weighted partial least squares regression (LW-PLSR) model (black-box model). LW-PLSR was utilized to cope with collinearity and nonlinearity. In the serial gray-box models, LW-PLSR models adjusted the fitting parameters of the white-box model depending on the process parameters for each query. In the parallel gray-box or combined gray-box models, LW-PLSR models compensated for the output error of the white-box or serial gray-box models, respectively. The results demonstrated that all three types of gray-box models improved the prediction accuracy of the white-box models regardless of the formulation. Besides, we proposed the assessment method based on Hotelling’s T2 and Q residual for gray-box models using LW-PLSR, which contributes decision support to select gray-box or white-box model. The accurate and descriptive gray-box models are expected to enhance process understanding and precise quality control in fluidized bed granulation.

著者

Yoshinari Hashimoto Yoshitaka Sawa Manabu Kano

出版者

The Iron and Steel Institute of Japan

雑誌

ISIJ International (ISSN:09151559)

巻号頁・発行日

vol.59, no.9, pp.1534-1544, 2019-09-15 (Released:2019-09-15)

参考文献数

27

被引用文献数

1 9

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Precise control of hot metal temperature (HMT) is crucial for achieving stable operation of a blast furnace, but it is difficult due to the sluggish dynamics caused by the huge heat capacity. To cope with such difficulty, this work aims at developing a method that can predict future HMT by adopting moving horizon estimation (MHE) based on a one-dimensional transient model. MHE is useful to successively adjust model parameters so that the undesirable influence of past disturbances on the prediction is minimized. The real application result demonstrated that the root mean square error (RMSE) of HMT of eight-hour-ahead prediction was only 11.6°C. The high-performance prediction enables operators to realize the efficient operation of the blast furnace.

著者

Keita Yaginuma Shuichi Tanabe Takuya Miyano Hiroshi Nakagawa Satoshi Suzuki Shuichi Ando Manabu Kano

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.68, no.9, pp.855-863, 2020-09-01 (Released:2020-09-01)

参考文献数

24

被引用文献数

3

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In-line monitoring of granule water content during fluid bed granulation is important to control drug product qualities. In this study, a practical scale-free soft sensor to predict water content was proposed to cope with the manufacturing scale changes in drug product development. The proposed method exploits two key ideas to construct a scale-free soft sensor. First, to accommodate the changes in the manufacturing scale, the process parameters (PPs) that are critical to water content at different manufacturing scales were selected as input variables. Second, to construct an accurate statistical model, locally weighted partial least squares regression (LW-PLSR), which can cope with collinearity and nonlinearity, was utilized. The soft sensor was developed using both laboratory (approx. 4 kg) data and pilot (approx. 25 kg) scale data, and the prediction accuracy in the commercial (approx. 100 kg) scale was evaluated based on the assumption that the process was scaled-up from the pilot scale to the commercial scale. The developed soft sensor exhibited a high prediction accuracy, which was equivalent to the commonly used near-infrared (NIR) spectra-based method. The proposed method requires only standard instruments; therefore, it is expected to be a cost-effective alternative to the NIR spectra-based method.

著者

Keita Yaginuma Shuichi Tanabe Hirokazu Sugiyama Manabu Kano

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.6, pp.548-556, 2021-06-01 (Released:2021-06-01)

参考文献数

22

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Soft sensors play a crucial role as process analytical technology (PAT) tools. They are classified into physical models, statistical models, and their hybrid models. In general, statistical models are better estimators than physical models. In this study, two types of standard statistical models using process parameters (PPs) and near-infrared spectroscopy (NIRS) were investigated in terms of prediction accuracy and development cost. Locally weighted partial least squares regression (LW-PLSR), a type of nonlinear regression method, was utilized. Development cost was defined as the cost of goods required to construct an accurate model of commercial-scale equipment. Eleven granulation lots consisting of three laboratory-scale, two pilot-scale, and six commercial-scale lots were prepared. Three commercial-scale granulation lots were selected as a validation dataset, and the remaining eight granulation lots were utilized as calibration datasets. The results demonstrated that the PP-based and NIRS-based LW-PLSR models achieved high prediction accuracy without using the commercial-scale data in the calibration dataset. This practical case study clarified that the construction of accurate LW-PLSR models requires the calibration samples with the following two features: 1) located near the validation samples on the subspace spanned by principal components (PCs), and 2) having a wide range of variations in PC scores. In addition, it was confirmed that the reduction in cost and mass fraction of active pharmaceutical ingredient (API) made the PP-based models more cost-effective than the NIRS-based models. The present work supports to build accurate models efficiently and save the development cost of PAT.

著者

Hayato Ishimoto Manabu Kano Hirokazu Sugiyama Hirofumi Takeuchi Katsuhide Terada Atsushi Aoyama Takuji Shoda Yosuke Demizu Jinen Shimamura Reiji Yokoyama Yuji Miyamoto Koji Hasegawa Masaru Serizawa Kazuomi Unosawa Kazuo Osaki Naochika Asai Yoshihiro Matsuda

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.2, pp.211-217, 2021-02-01 (Released:2021-02-01)

参考文献数

27

被引用文献数

3

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As a result of the research activities of the Japan Agency for Medical Research and Development (AMED), this document aims to show an approach to establishing control strategy for continuous manufacturing of oral solid dosage forms. The methods of drug development, technology transfer, process control, and quality control used in the current commercial batch manufacturing would be effective also in continuous manufacturing, while there are differences in the process development using continuous manufacturing and batch manufacturing. This document introduces an example of the way of thinking for establishing a control strategy for continuous manufacturing processes.

著者

Hayato Ishimoto Manabu Kano Hirokazu Sugiyama Hirofumi Takeuchi Katsuhide Terada Atsushi Aoyama Takuji Shoda Yosuke Demizu Jinen Shimamura Reiji Yokoyama Yuji Miyamoto Koji Hasegawa Masaru Serizawa Kazuomi Unosawa Kazuo Osaki Naochika Asai Yoshihiro Matsuda

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

pp.c20-00824, (Released:2020-12-08)

参考文献数

27

被引用文献数

3

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As a result of the research activities of the Japan Agency for Medical Research and Development (AMED), this document aims to show an approach to establishing control strategy for continuous manufacturing of oral solid dosage forms. The methods of drug development, technology transfer, process control, and quality control used in the current commercial batch manufacturing would be effective also in continuous manufacturing, while there are differences in the process development using continuous manufacturing and batch manufacturing. This document introduces an example of the way of thinking for establishing a control strategy for continuous manufacturing processes.