scholarly journals 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 ◽  
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.

scholarly journals Advanced Process Analytical Technology in Combination with Process Modeling for Endpoint and Model Parameter Determination in Lyophilization Process Design and Optimization

Processes ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1600
Author(s):  
Alex Juckers ◽  
Petra Knerr ◽  
Frank Harms ◽  
Jochen Strube
Keyword(s):  
Process Design ◽  
Quality By Design ◽  
Process Development ◽  
Process Analytical Technology ◽  
Parameter Determination ◽  
Design And Optimization ◽  
Manometric Temperature Measurement ◽  
Analytical Technology ◽  
Main Shortcoming

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.

scholarly journals Digital Twin for Extraction Process Design and Operation

Processes ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. 866 ◽  
Author(s):  
Lukas Uhlenbrock ◽  
Christoph Jensch ◽  
Martin Tegtmeier ◽  
Jochen Strube
Keyword(s):  
Process Analytical Technology ◽  
Extraction Process ◽  
Process Models ◽  
Advanced Process Control ◽  
Manufacturing Optimization ◽  
Innovative Methods ◽  
Digital Twins ◽  
Extraction Processes ◽  
Regulated Industries ◽  
Analytical Technology

Traditional extraction processes of natural product are widespread, especially in regulated industries. Possibilities of extraction development and manufacturing optimization in regulated industries is limited. Regulatory approvals are often based on traditional preparations of phyto-pharmaceuticals. The dependence on traditional processes can result in sub-optimal extraction parameters causing unnecessary costs and product variability. Innovative methods like Quality-by-Design (QbD), including process analytical technology (PAT), open opportunities for manufacturers to cope with regulatory demanded, narrow batch-to-batch variability. In addition, such validated process models represent perfect digital twins which could be utilized for advanced process control and life cycle analysis.

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

Processes ◽  
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.

Process Analytical Technology for Online Monitoring of Organic Reactions by Mass Spectrometry and UV–Vis Spectroscopy

2018 ◽  
Vol 96 (1) ◽  
pp. 124-131 ◽  
Author(s):  
Patrick W. Fedick ◽  
Robert L. Schrader ◽  
Stephen T. Ayrton ◽  
Christopher J. Pulliam ◽  
R. Graham Cooks
Keyword(s):  
Mass Spectrometry ◽  
Online Monitoring ◽  
Process Analytical Technology ◽  
Organic Reactions ◽  
Vis Spectroscopy ◽  
Analytical Technology

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

Talanta ◽  
2014 ◽  
Vol 120 ◽  
pp. 114-125 ◽  
Author(s):  
Cédric Schaefer ◽  
David Clicq ◽  
Clémence Lecomte ◽  
Alain Merschaert ◽  
Edith Norrant ◽  
...  
Keyword(s):  
Manufacturing Process ◽  
Process Development ◽  
Process Analytical Technology ◽  
Analytical Technology
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