Advanced process control in biopharmaceutical production

Process models form the basis for advanced control strategies in bio-pharmaceutical process. ABB helps set up PAT-enabled model-based control of a fed-batch mammalian cell culture. These advanced strategies can increase productivity and process robustness, as well as decrease process variation.

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A wide range of potential applications

The biopharmaceutical sector has become a significant and growing division of the pharmaceutical industry, with the the top-selling drugs being protein-based products. Mammalian cells, particularly Chinese hamster ovary (CHO) cells, and bacterial systems, such as Escherichia coli (E. coli), produce the bulk of the products on the market but alternative systems such as yeast and plant cells are also used.

Utilizing ABB’s xPAT product, ABB collaborated with Irish universities and leading biopharmaceutical players in an initiative funded by Enterprise Ireland to construct models to set up and evaluate the benefits of PAT-enabled, model-based control of a fed-batch mammalian cell culture.

There is a wide range of potential applications for models of the mammalian cell culture process: investigation of underlying process mechanisms; analysis and prediction of experimental results facilitating swifter process optimization; advanced control strategies; decision support systems; and soft sensors. Choice of model type depends on both the intended application and also the quantity, quality and nature of experimental data available upon which to build the model.
Biopharmaceutical production takes place in inordinately complex environments, with a nonlinear, dynamic mix of billions of cells and nutrients, vulnerable to temperature change, pH, inhomogeneity and so on.

Model predictive control - inherently suited to optimization

Once the effort to build a good process model has been expended, it is desirable to exploit that model to maximize the benefit. Model-based control strategies represent one potential application. There are numerous forms of model-based control including model predictive control (MPC).

MPC is a multiple-input multiple-output (MIMO) control algorithm based on the repeated solution of a finite-horizon optimal control problem subject to a performance specification, constraints on states and inputs, and a system model. It can use a mathematical model such as first principle or neural network models, or statistical models such as PCA or PLS to create a future trajectory of the batch based on multiple measured process inputs.

It seeks to minimize the square of the error between the predicted trajectory and desired trajectory over a userdefined prediction horizon and then calculates a controller action for each of its outputs. In contrast to a traditional PID controller, which aims to minimize the instantaneous error between process variable and setpoint, the longer view taken by MPC reduces the impact of unknown disturbances, erratic signals and noise. MPC can also deal well with systems with a long dead time, though it is not robust in situations where the dead time changes significantly. MPC is inherently suited to optimization.

The presence of a dynamic optimizer, objective function and constraints within the framework means that MPC can predict future violations of constraints, handle complex interactions and smoothly adjust the manipulated variables. MPC has the widest application of all advanced control strategies in industrial applications.
The longer view taken by MPC reduces the impact of unknown disturbances, erratic signals and noise. MPC can also deal well with systems with a large dead time.

An online real-time process control system

The Process Analytical Technology (PAT) initiative launched by US Food and Drug Administration (FDA) aims to design quality into the process, rather than relying on testing the CQAs of the final product. Statistical models can be used as an aid for online process evaluation and decision making, as well as a tool for identifying variables likely to be responsible for deviations.

An industry-specific application built on ABB's System 800xA infrastructure, xPAT (eXtended PAT) is a next-generation PAT solution that harnesses the System 800xA operations and engineering environment and integration capability to provide significant improvements in the overall process and end-product quality. It provides life sciences users with a single system to access and examine online, real-time process data directly from the manufacturing operation.

The configurable Windows-based system collects data from ABB and/or third-party vendors’ analytical instruments and analyzes the data to determine the actual condition of the process. It then passes the resulting information to the ABB or third-party control system, and to other applications that support the drug manufacturing process.
Statistical models can be used as an aid for online process evaluation and decision making, as well as a tool for identifying variables likely to be responsible for deviations
ABB’s integrated PAT solution

Learn more

Model predictive control demystified

Reference case studies

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Search criteria provided no results

There are There is 1 results listed below result listed below

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