Pharma 4.0 Continuous mRNA Drug Products Manufacturing

Area of Science:

• Pharmaceutical Manufacturing
• Biotechnology
• Process Engineering

Background:

• Continuous manufacturing of mRNA drugs offers advantages like quality by design and automation but faces challenges in process understanding and high development costs.
• Transitioning from batch to continuous processes requires a holistic understanding and overcoming financial barriers associated with pilot line development.

Purpose of the Study:

• To hierarchically design continuous bioprocesses for scalable, end-to-end sterile mRNA production using digital tools.
• To analyze resource commitment and identify key cost drivers in continuous mRNA manufacturing.

Main Methods:

• Utilized Systems-based Pharmaceutics 4.0 digital design tools, including mass/energy balance simulations, Monte-Carlo machine learning, and spatial analysis.
• Developed and validated a continuous, end-to-end process for sterile mRNA formulation into lipid nanocarriers.
• Conducted resource commitment analysis to identify major cost factors.

Main Results:

• Demonstrated the first feasible continuous, end-to-end production of sterile mRNA formulated into lipid nanocarriers.
• Defined equipment specifications and operational space for the continuous bioprocess.
• Identified cell lysis modules (40% equipment cost) and linearization enzymes (42% raw material cost) as principal resource-intensive factors.

Conclusions:

• Digital design tools enable the overcoming of barriers in continuous mRNA manufacturing, facilitating scalable and robust processes.
• The developed continuous process offers a cost-effective solution with low margin lifecycle fluctuation (MSPD 1.30-1.45 €).
• Understanding and optimizing resource-intensive steps like cell lysis and enzyme usage are crucial for economic viability in continuous mRNA production.