Breakthroughs in Bioprocess Modeling and Control

by , | Jun 2, 2021 | Life Sciences & Medical, Simulation

Jim Cahill

Chief Blogger, Social Marketing Leader

Biopharmaceutical manufacturers have done amazing work in getting the COVID-19 vaccines out across the globe. Bioprocessing of these and other medicines is performed in bioreactors which rely on cells to create the intended therapeutic.

New Directions in Bioprocess Modeling and ControlEmerson’s Greg McMillan, teaming with Christopher Stuart, Rehman Fazeem, Zachary Sample and Timothy Schieffer have updated and revised the second edition of the book, New Directions in Bioprocess Modeling and Control. I had the opportunity to get an advanced look at this soon-to-be available book, now available for preorder.

In the preface, the authors highlight the technology breakthroughs since the first edition, which:

…can potentially revolutionize advances in bioprocess performance. The modeling breakthroughs include new simple equations that can be easily initialized and continuously improved to model the effect of the concentrations of all components, temperature, and pH on cell growth rate and product performance rate. The automation breakthroughs include an enhanced proportional-integral-derivative (PID) controller that enables the use of at-line and off-line analyzers for closed-loop control growth rate and production rate. The enhanced PID controller is simple to implement, easy to tune, and amazingly resilient to measurement failures and increases in analysis time. To support these breakthroughs are blocks to model automation system dynamics, measure system performance, compute batch slopes, predict endpoints, and rapidly estimate PID tuning settings…

I’ll highlight one example of a breakthrough, the synergy of real-time modeling systems (RTMS) with digital twin simulation. A full explanation is found in N.7 in Appendix N: Debottlenecking Using Sensitivity Analysis.

Once the debottlenecking pathway has been determined, it is a natural extension to use the RTMS with a Mimic Dynamic simulation in the digital twin to evaluate the most efficient manner of alleviating the bottleneck. The debottlenecking pathway identifies and quantifies the target cycle time reductions required to resolve the impasse, and a digital twin can provide the detailed automation modifications to be deployed. For example, the digital twin can show the benefit of more precise control valves and sensors, middle signal selection, and computations by using existing measurements to diagnose and predict abnormal operations and provide procedure automation to proactively minimize disruption.

To give you a flavor for the content, here are the chapters and appendices:

  1. Opportunities
  2. Dynamics
  3. Basic Control
  4. Model-Predictive Control
  5. Digital Twin
  6. First-Principle Models
  7. Analytical Technologies
  8. Data Analytics
  9. Models to Improve Operator, Automation, and Process Performance
  1. Automation System Performance Top 10 Concepts
  2. Bioprocess Biology
  3. Enhanced PID Controller for Wireless and Analyzer Applications
  4. Modern Myths
  5. Enzyme Inactivity Decreased by Controlling the pH with a Family of Bezier Curves
  6. First-Principle Process Relationships
  7. Gas Pressure Dynamics
  8. Charge Balance to Model pH
  9. Interactive to Noninteractive Time Constant Conversion
  10. Jacket and Coil Temperature Control
  11. PID Forms and Conversion of Tuning Settings
  12. Liquid Mixing Dynamics
  13. Mammalian Bioreactor Model
  14. Debottlenecking Using Sensitivity Analysis

If you work with bioprocesses, visit the ISA.org website to order your copy of this book. The Life Sciences & Medical section on Emerson.com also has more on the technologies and solutions to help you drive improved business performance.

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The opinions expressed here are the personal opinions of the authors. Content published here is not read or approved by Emerson before it is posted and does not necessarily represent the views and opinions of Emerson.