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Quality by Control – Advanced monitoring and control solution for bioprocesses

The state-of-the-art for process control and quality assurance in biopharmaceutical manufacturing is based on a static Quality by Testing approach. The production process is fixed and tightly specified to guarantee a constant and defined product quality which is verified by intensive testing. Exceeding the specification ranges of such processes results in rejection of batches and consequently leads to increased consumption of raw material and energy. In 2002 the US Food and Drug Administration started the Process Analytical Technology (PAT) initiative, aiming to guide the industry towards more dynamic manufacturing processes. PAT is focusing on the identification of Critical Process Parameters affecting the product’s Critical Quality Attributes and subsequently their real-time monitoring and control.

Quality cannot be tested into products;
it should be built-in or should be by design.

US Food and Drug Administration (FDA) 

However, these quality attributes are usually not directly measurable. The proposed strategy to be followed is to employ complex on-line analyzer systems (f.i. 2D fluorescence spectroscopy or Raman spectroscopy) in combination with mathematical techniques to build up correlations between nonspecific signals and process variables for real-time estimation of process performance and product quality.

Schematic illustration of Quality by Design benefits

Schematic illustration of the variable inputs of a bioprocess as well as the link between critical process parameters and quality attributes.

The main hurdle of this approach is the implementation of advanced sensor systems, delivering hundreds or thousands of values at each measurement, to the Advanced Process Control (APC) system. This includes data storage, pre-processing and data alignment in a GMP/GAMP5 (category 4) conform manner. 

With the University of Natural Resources and Life Sciences Vienna as a research partner, Bilfinger Industrietechnik Salzburg is working on a fully integrated PAT and Advanced Process Control (APC) add-in for its control system. It allows easy integration of several advanced sensor systems. Furthermore it is capable of performing time-alignments with other process relevant measurements and even off-line measured values. The gathered data can easily be compared and batch-wise exported, to perform statistical analyses or create mathematical models.

In order to meet the PAT initiative’s intention, the built models in combination with the on-line data can be used in real-time to calculate key figures and estimators (soft-sensors). Following the control perspective of the PAT initiative, our Quality by Control (QbC) add-on is capable of closing the loop and using the estimators for real-time APC including model predictive control (MPC).

Advanced process control concept

Conventional process control and the Bilfinger’s advanced process control concept.

At the moment, the new add-ins are in their final step of development and in-house testing. A beta-version will be launched by the end of 2018. We want to provide our customers with expertise in PAT implementation and a software platform capable to perform innovative and advanced process monitoring and control.

Research Partner

University of Natural Resources and Life Sciences
Vienna
Department of Biotechnology
Research Group Striedner

 


Quality by Control – Objectives

Fully automated software platform for data-integration, -processing and -management, modeling and control

Predictive process models

MPC and advanced process automation

In-process product quality control

Get in contact

If you are interested in our PAT/APC solution or in testing please contact us:

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Funding

This project is funded by the Austrian Research Promotion Agency (FFG).