A Process Analytical Technology (PAT) approach to control a new API manufacturing process: Development, validation and implementation

Lyophilization is widely used in the preservation of thermolabile products. The main shortcoming is the long processing time. Lyophilization processes are mostly based on a recipe that is not changed, but, with the Quality by Design (QbD) approach and use of Process Analytical Technology (PAT), the process duration can be optimized for maximum productivity while ensuring product safety. In this work, an advanced PAT approach is used for the endpoint determination of primary drying. Manometric temperature measurement (MTM) and comparative pressure measurement are used to determine the endpoint of the batch while a modeling approach is outlined that is able to calculate the endpoint of every vial in the batch. This approach can be used for process development, control and optimization.

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Antibody Concentration Measurement Using Optical Rotation: Toward Process Analytical Technology

MATEC Web of Conferences ◽

10.1051/matecconf/202133315002 ◽

2021 ◽

Vol 333 ◽

pp. 15002

Author(s):

Hidenori Inaba ◽

Kosuke Wakabayashi ◽

Ikuo Tsujimoto ◽

Noriko Yoshimoto ◽

Shuichi Yamamoto

Keyword(s):

Cell Culture ◽

Manufacturing Process ◽

Process Analytical Technology ◽

Optical Rotation ◽

Pharmaceutical Products ◽

Antibody Concentration ◽

Purification Process ◽

Rotation Method ◽

Wide Range ◽

Analytical Technology

The antibody manufacturing process consists of the cell culture process using animal cells and the purification process including several chromatography steps and filtration steps. The purification process is important to obtain high quality bio-pharmaceutical products by removing impurities, and measurement of antibody concentrations is a fundamental and essential factor to control the manufacturing process and to confirm the yield of each purification step. Here we introduce the optical rotation method as a resolution for measuring antibody concentrations in the manufacturing process. Feasibility evaluation showed that optical rotation is applicable for measuring a wide range of antibody concentrations even in cell culture supernatants containing various contaminants. In addition, as examples of application to the process analytical technology, we show the possibility of the optical rotation method in the continuous cell culture and chromatography process, and the tangential flow filtration concentration process.

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Towards Autonomous Operation by Advanced Process Control—Process Analytical Technology for Continuous Biologics Antibody Manufacturing

Processes ◽

10.3390/pr9010172 ◽

2021 ◽

Vol 9 (1) ◽

pp. 172

Author(s):

Heribert Helgers ◽

Axel Schmidt ◽

Lara Julia Lohmann ◽

Florian Lukas Vetter ◽

Alex Juckers ◽

...

Keyword(s):

Process Control ◽

Product Quality ◽

Process Development ◽

Process Analytical Technology ◽

Control Process ◽

Continuous Manufacturing ◽

Two Phase ◽

Advanced Process Control ◽

Vis Spectroscopy ◽

Analytical Technology

Continuous manufacturing opens up new operation windows with improved product quality in contrast to documented lot deviations in batch or fed-batch operations. A more sophisticated process control strategy is needed to adjust operation parameters and keep product quality constant during long-term operations. In the present study, the applicability of a combination of spectroscopic methods was evaluated to enable Advanced Process Control (APC) in continuous manufacturing by Process Analytical Technology (PAT). In upstream processing (USP) and aqueous two-phase extraction (ATPE), Raman-, Fourier-transformed infrared (FTIR), fluorescence- and ultraviolet/visible- (UV/Vis) spectroscopy have been successfully applied for titer and purity prediction. Raman spectroscopy was the most versatile and robust method in USP, ATPE, and precipitation and is therefore recommended as primary PAT. In later process stages, the combination of UV/Vis and fluorescence spectroscopy was able to overcome difficulties in titer and purity prediction induced by overlapping side component spectra. Based on the developed spectroscopic predictions, dynamic control of unit operations was demonstrated in sophisticated simulation studies. A PAT development workflow for holistic process development was proposed.

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Development of a General PAT Strategy for Online Monitoring of Complex Mixtures—On the Example of Natural Product Extracts from Bearberry Leaf (Arctostaphylos uva-ursi)

Processes ◽

10.3390/pr9122129 ◽

2021 ◽

Vol 9 (12) ◽

pp. 2129

Author(s):

Christoph Jensch ◽

Larissa Knierim ◽

Martin Tegtmeier ◽

Jochen Strube

Keyword(s):

Online Monitoring ◽

Process Development ◽

Process Analytical Technology ◽

Complex Mixture ◽

Complex Mixtures ◽

Data Set ◽

Methodical Approach ◽

Extraction Processes ◽

First Time ◽

Analytical Technology

For the first time, a universally applicable and methodical approach from characterization to a PAT concept for complex mixtures is conducted—exemplified on natural products extraction processes. Bearberry leaf (Arctostaphylos uva-ursi) extract is chosen as an example of a typical complex mixture of natural plant origin and generalizable in its composition. Within the quality by design (QbD) based process development the development and implementation of a concept for process analytical technology (PAT), a key enabling technology, is the next necessary step in risk and quality-based process development and operation. To obtain and provide an overview of the broad field of PAT, the development process is shown on the example of a complex multi-component plant extract. This study researches the potential of different process analytical technologies for online monitoring of different component groups and classifies their possible applications within the framework of a QbD-based process. Offline and online analytics are established on the basis of two extraction runs. Based on this data set, PLS models are created for the spectral data, and correlations are conducted for univariate data. In a third run, the prediction potential is researched. Conclusively, the results of this study are arranged in the concept of a holistic quality and risk-based process design and operation concept.

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