Continuous Bioprocess Control for Integrated Therapeutic Protein Production
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Solution Overview
Problem
Existing continuous bioprocesses for producing therapeutic proteins lack integration and communication between unit operations, often relying on offline chromatography with limited feedback, leading to inefficiencies and challenges in scalability from laboratory to manufacturing scale.
Innovation Solution
An automated integrated continuous bioprocess system with a master controller for process regulation, incorporating a bioreactor, alternating tangential flow filter, multiple chromatography systems, viral inactivation, and a control system for seamless operation, including SCADA, PID, PLC, and DCS, enabling uninterrupted production and scalability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If batch processing is used for therapeutic protein manufacturing, then process control is simple, but productivity is low and cycle time is long
Solution Approach 1:
The patent merges multiple standalone unit operations into an integrated continuous manufacturing system where the bioreactor, chromatography systems, viral inactivation, and filtration are connected in sequence with automated control, enabling continuous processing without batch interruptions while maintaining coordinated process control through a central control system
Solution Approach 2:
The system implements continuous processing where the therapeutic protein flows continuously through bioreactor cultivation, ATF filtration, chromatography purification, viral inactivation, and final filtration without batch interruptions, eliminating idle time between operations and maintaining continuous productive action throughout the manufacturing process
2Volume of stationary object
If pseudo-continuous process with standalone units is used, then equipment size is reduced, but communication between unit operations is limited and feedback is insufficient
Solution Approach 1:
The patent implements real-time feedback through a central control system that continuously monitors process parameters (flow rates, pressures, temperatures, pH) from sensors throughout the system and automatically adjusts operational parameters to maintain optimal conditions, ensuring information flows bidirectionally between all unit operations and the control system
Solution Approach 2:
The control system serves multiple functions simultaneously: it monitors process parameters, controls pumps and valves, regulates chromatography gradients, manages viral inactivation conditions, and coordinates filtration operations, making a single control system perform all regulatory functions across the entire continuous manufacturing process
3Device complexity
If offline chromatography analysis is used, then equipment complexity is reduced, but manufacturing precision and quality control are limited
Solution Approach 1:
The patent replaces offline mechanical chromatography analysis with online analytical detection systems that continuously monitor protein purification in real-time using sensors and detectors integrated into the flow path, eliminating the need for separate offline analysis steps while providing continuous quality data
4Loss of time
If batch processing is used, then process control is simplified, but cycle time is long and productivity is low
Solution Approach 1:
The system employs dynamic control where operational parameters such as flow rates, chromatography gradients, and pH levels are continuously adjusted in real-time based on feedback from process sensors, allowing the system to adapt to changing conditions while maintaining continuous operation and optimal performance throughout the manufacturing process
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
Facilitates uninterrupted and scalable production of therapeutic proteins by maintaining process parameters and integrating unit operations, enhancing yield and quality through real-time feedback and automation.
Implementation Method 1
the bioreactor (103) enabled with alternating tangential flow (ATF) filter (109) to collect a harvest comprising the protein secreted into the culture medium
Implementation Method 2
a first chromatography system (119) connected to the ATF filtration system (109) of the bioreactor (103) without any intermediate hold vessel to purify the harvested recombinant therapeutic protein
Implementation Method 3
a viral inactivation system (126) including a viral inactivation vessel (128) connected to the a first chromatography system (119) to collect the protein A eluate and inactivate viruses that may be present in the eluate
Implementation Method 4
the viral inactivation vessel (128) configured to automatically adjust pH of the protein A eluate
Implementation Method 5
a collection vessel (136) connected with the viral inactivation vessel (128) through one or more filters to receive the virus inactivated, neutralized, and filtered protein A eluate, wherein said one or more filter(s) (224) and (226) are configured to remove impurities in the form of precipitates
Data Source
AI summary
The present invention relates to an automated integrated continuous bioprocess system and bioprocess that are capable of continuously producing therapeutic protein in an uninterrupted manner and scalable from laboratory to manufacturing scale. The present invention provides an automated integrated continuous bioprocess system and bioprocess for producing therapeutic protein, in which the system and process is controlled with one or more control system selected from supervisory control and data acquisition (SCADA) control system (110), proportional integral derivative (PID), programmable logic circuit (PLC), industrial PC (IPC), distributed control system (DCS), message relaying system and automated UPLC/HPLC sampling for online testing to run the system and process and in an uninterrupted manner and continuously produce therapeutic protein.