Refolding Project

Using the refolding step, it should be shown how an increase in product yields can be achieved with the help of the digital twin following the enhanced approach of the ICH Q12 guideline.

In cooperation with the Vienna University of Technology (TU Wien), Bilfinger Life Science is developing a platform technology for refolding of inclusion bodies started in 2019 (following a project initiated in 2018 – Controlled refolding of inclusion body protein to boost product yields). In a second step of the project previous and following process steps will be included in the process model and last the process will be switched from batch to continuous mode.


Control of the refolding process using Digital Twin and Qubicon.


Aim of the project:

Development of a process unit for the refolding step with advanced process monitoring and control


  • Allow monitoring and controllability during refolding process
  • Reduce misfolding and agglomeration of product
  • Increase product yield and STY (space time yield)
  • Reduce volume
  • Allow scalability
  • Modular bioprocess solutions for automated and optimized integrated refolding processes


  • Advanced process monitoring and control using Bilfinger software
  • Implement mathematical models and soft-sensors
  • Real-time KPI calculations
  • User-defined control strategies
  • Data visualization and management in a central database



  • Analysis of influencing factors on refolding yield
  • Comparing suitability of PAT tools for process monitoring
  • Proof of concept: Digital twin can follow the process and predict refolding yields in real time
  • Product design for refolding unit


  • Proof of concept: Digital twin can follow the refolding process to achieve optimum yield and Sty according to the users’s needs
  • Pilot process unit with advanced process monitoring and control available
  • Demonstration of the automated refolding process chain to reach higher STY
  • Control of refolding processes in fed-batch mode
  • Transfer of process to alternative model proteins


  • Beta tester
  • Proof of concept: Digital twin works for continuous refolding processes along the entire process chain

Project manager

Bernhard Sissolak
Head of Innovation Pharma



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