Continuous Recombinant Protein Manufacturing With Single-Use Modules
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Solution Overview
Problem
Current continuous cell-culture systems suffer from scalability issues and low production yield, necessitating an alternative system that addresses these limitations.
Innovation Solution
An integrated, automated, single-use system comprising a bioreactor, tangential flow filtration, column chromatography, tankless hold, and virus inactivation plug flow reactor, connected via tubing and pumps, capable of processing recombinant proteins efficiently.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If current continuous cell-culture systems are used, then production can be maintained, but scalability is limited and production yield is low
Solution Approach 1:
The system is divided into separate single-use modules (bioreactor, TFF system, chromatography columns, virus inactivation reactor) that can be independently configured and scaled. Each module processes a specific function, allowing the overall system to be scaled by adjusting individual module capacities rather than redesigning the entire system.
Solution Approach 2:
The system employs dynamic control of flow rates, residence times, and operational parameters through automated pumps and control systems. This allows the system to adapt to different production scales and maintain optimal performance across varying production volumes from 10g to 5000g per day.
2Extent of automation
If traditional multi-use systems with tanks are used, then equipment can be reused, but system complexity increases and automation becomes more difficult
Solution Approach 1:
The system uses single-use disposable bags and modules that are discarded after one production run. This eliminates the need for complex cleaning, sterilization, and maintenance systems, significantly reducing overall system complexity while enabling straightforward automation. Each single-use module is pre-sterilized and ready for immediate use.
Solution Approach 2:
The system extracts and eliminates the complex tank infrastructure from traditional bioprocessing systems. By using single-use bags with integrated ports and connections, the patent removes the need for multi-port tank assemblies, complex valve systems, and extensive piping, thereby simplifying the overall system architecture.
3Productivity
If continuous processing is implemented, then productivity increases, but maintaining consistent product quality becomes more challenging
Solution Approach 1:
The system maintains continuous processing throughout all stages from cell culture through purification to virus inactivation. This continuous operation eliminates batch-to-batch variations and maintains consistent product quality through steady-state processing conditions, while maximizing productivity by avoiding downtime between batches.
Solution Approach 2:
The system incorporates automated monitoring and control systems that continuously measure process parameters (flow rates, pressures, temperatures, conductivity) and provide feedback to maintain optimal processing conditions. This ensures consistent product quality by automatically correcting deviations from target parameters in real-time.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The system achieves a 500-fold dynamic range in processing capacity, enabling scalable production of recombinant proteins from 10 g to 5,000 g per day with consistent product quality, overcoming the limitations of existing systems.
Implementation Method 1
a single-use tangential flow filtration system
Implementation Method 2
a single-use dual-column capture column chromatography skid
Implementation Method 3
a single-use virus inactivation plug flow reactor
Data Source
AI summary
Integrated systems and methods for the manufacturing of recombinant proteins in mammalian cells are provided. The systems and methods include a single-use bioreactor (SUB), a tangential flow filtration system, a column chromatography skid, a tankless hold, a virus inactivation plug flow reactor, and pumps.