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)

Christoph Jensch,Larissa Knierim,Martin Tegtmeier,Jochen Strube

doi:10.3390/pr9122129

Abstract

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.

Highlights

The quality by design (QbD) approach on process development has its background in the pharmaceutical industry
The core aspects of this process design method, process robustness, and process understanding paired with cleverly implemented digital twins and process analytical technologies (PAT) leading towards advanced process control (APC) based on model predictive control and process status evaluation, can be beneficial for every field of process industry
As already mentioned in the introduction, the creation of digital twins, digital twinbased evaluation of a process status, and the implementation possibilities of design spaces were already conducted in previous studies [9,10,16,17,52]

Summary

Introduction

The quality by design (QbD) approach on process development has its background in the pharmaceutical industry. The regulatory environment sets the framework, as traditional approvals are tied to manufacturing processes, which limits the possibilities for further development of the processes or optimization of operations. The associated dependence on traditional manufacturing processes can lead to the fact that raw materials are not optimally utilized through the selection of suboptimal process parameters. Traditional extraction processes can lead to high process variabilities and bad process stability [8]. Innovative methods such as Quality by Design including Process Analytical Technology offer opportunities for manufacturers to meet regulatory requirements such as low product variability between production batches [9,10]

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Conclusion