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

Advantages:

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

Novelty:

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

Milestones:

2021

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

2022

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

2023