Perfusion Bioreactor Reference Data for Cell Culture Quality Prediction
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Solution Overview
Problem
Current predictive models for controlling quality attributes in cell cultures are limited by insufficient and unreliable historical data, leading to inadequate control over product quality due to insufficient sampling frequency and dynamic model development.
Innovation Solution
A method and system for generating efficient and reliable reference data using a perfusion bioreactor to control quality attributes, where attribute influencing parameters are varied over time to determine corresponding quality attribute changes, allowing for the creation of predictive models that can forecast future quality attribute concentrations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If manual sampling and analysis is performed to monitor quality attributes, then product quality can be assessed, but the sampling frequency is insufficient to develop dynamic models required for control strategies
Solution Approach 1:
The patent replaces manual sampling and analysis with automated in-line sensing and monitoring systems that continuously measure quality attributes and process parameters. This substitution enables high-frequency data collection without the limitations of manual operations, providing sufficient resolution to develop dynamic models for predictive control.
2Reliability
If historical data is used to develop predictive models, then model development can proceed with existing information, but the data is insufficient and unreliable due to various anomalies in individual cell cultures
Solution Approach 1:
The patent implements continuous monitoring and data collection throughout the cell culture process, capturing quality attributes and process parameters at all stages. This continuous action generates comprehensive, anomaly-free datasets that are sufficient for developing reliable predictive models, eliminating the limitations of sparse historical data.
Solution Approach 2:
The system incorporates real-time feedback loops where measured quality attributes and process parameters are continuously fed back into the predictive models. This feedback mechanism allows the models to be continuously refined and validated against actual process outcomes, improving their reliability and accuracy.
3Loss of time
If batch processes are used to grow cell cultures, then the biological material remains in the bioreactor until the end of reaction time, but problems are identified too late to enact successful remedial action
Solution Approach 1:
The patent employs predictive models that forecast future quality attribute values based on current process data. By predicting quality outcomes before they actually occur, the system enables preliminary corrective actions to be taken in advance, preventing quality deviations rather than responding to them after detection.
Solution Approach 2:
The system implements real-time feedback control where measured process parameters and quality attributes are continuously monitored and fed back to adjust process conditions. This closed-loop control enables timely remedial actions to maintain product quality within specifications throughout the batch process.
Data Source
AI summary
A process and system for efficiently producing reference data that can be fed into a predictive model for predicting quality attribute concentrations in cell culture processes. A perfusion bioreactor is operated at pseudo-steady-state conditions and one or more attribute influencing parameters are manipulated and changed over time. As the one or more attribute influencing parameters are manipulated, one or more quality attributes are monitored and measured. In one embodiment, multiple quality attributes are monitored and measured in parallel. The quality attribute information is recorded in conjunction with the changes in the attribute influencing parameters. This information is then fed to the predictive model for propagating cell cultures in commercial processes and maintaining the cell cultures within desired preset limits.