Work Package 3

Advancing scientific capacity of IST in digitalization of biomanufacturing ​

Instituto Superior Técnico

OBJECTIVES

Main Goals:

“How to incorporate a digitalization framework in the conceptual design, research and development of biomanufacturing processes”?

TEST BED

Escherichia coli-based processes for the biomanufacturing of plasmid DNA including both upstream (e.g., cell culture and plasmid amplification) and downstream processing (e.g., recovery, intermediate isolation and purification) operations.

MAJOR GOAL

To establish a working, lab scale manufacturing process and its corresponding in-silico representation.

WORKFLOW

TASKS

3.1. Setting up of an upstream benchmark process​

Lead: IST
Duration: M13-M15​

Aims to define the E. coli strains and model plasmids that will be tested, to outline an upstream benchmark process for the production of pDNA, and set up key analytics.

3.2. Modelling of cell growth and pDNA amplification​

Lead: DTU
Duration: M14-M22​

Aims at creating mathematical models for producing pDNA using E. coli.  The process involves selecting an appropriate model structure that aligns with biological and physical nuances, using data from task 3.1.​

3.3. High-throughput screening of culture conditions​

Lead: TUB
Duration: M16-M24​

Aims to screen for process conditions (e.g., growth conditions, media composition) that maximise the performance of the model cell/plasmid system (task 3.1) using an automated high throughput screening platform, guided by the predictive models developed by DTU (task 3.2)

3.4. Downstream processing of pDNA​

Lead: IST
Duration: M17-M24​

Aims to establish a working downstream processing scheme for the purification of plasmid DNA. Key data will be generated at IST that will then be used by DTU to develop digital models of the operations in Task 3.5.​

3.5. Modelling of the downstream processing of pDNA​

Lead: DTU
Duration: M19-M27​

Aims at the development and application of mathematical models, particularly mechanistic and hybrid forms, to describe the isolation and purification of pDNA from E. coli cells.

3.6. Holistic process characterization

Lead: TUB
Duration: M25-M33

Aims at performing a holistic upstream and downstream process characterization, by assessing how upstream influences the downstream processing performance. ​

3.7. Model integration and process validation​

Lead: DTU
Duration: M30-M36​

Aims to merge models describing both upstream and downstream processing sections into a singular, unified model, and  to rigorously validate this consolidated model at the 1-2 L lab scale, ensuring it reflects real system dynamics.

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